sort by

292 publications mentioning hsa-mir-206 (showing top 100)

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-206. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 520
Second, miR-206 can directly regulate mRNA expression by targeting the 3′-UTR of MET and BCL2, and inhibit protein expression of cyclin D1 and gene expression of cyclin D1, cyclin D2 and matrix metalloproteinase 9 (MMP-9), while increased p57 gene expression in lung cancer cell (A549). [score:15]
In this study, we show for the first time that miR-206 directly targets and regulates the full-length 3′-UTR of the human BCL2 (B-cell lymphoma-2) gene, and confirmed that miR-206 directly targets and regulates the full-length 3′-UTR of the human MET mRNA, which are up-regulated in many cancers, including lung cancer. [score:12]
As expected, miR-206 mimic treated cells showed higher expression of miR-206 than blank A549 or SK-MES-1 cells, and miR-206 inhibitor inhibited miR-206 expression (Fig. 5A and 5B). [score:9]
The growth -inhibition role of miR-206 may attribute to that miR-206 targets 3′-UTR of MET mRNA, and inhibits the expression of MET in lung cancer cells. [score:9]
Ectopic expression of miR-206 inhibits c-Met, Bcl2, cyclin D1, cyclin D2 and MMP-9, and inhibits p57 expression in A549 and SK-MES-1 cells. [score:9]
For convenience, has-miRNA-206 mimic and mimic negative control, has-miRNA-206 inhibitor and inhibitor negative control were simply referred to as miR-206 mimic and miR mimic NC, miR-206 inhibitor and miR inhibitor NC, respectively. [score:9]
Evidence of miR-206 as a tumor growth suppressor has been reported in several cancers: miR-206 was found down-regulated in ERα -positive human breast cancer tissues and transfection of miR-206 into MCF-7 breast cancer cells inhibits cell growth in a dose- and time -dependent manner [30]. [score:8]
Moreover, up-regulation of miR-206 suppresses lung cancer cell migration, invasion and colony formation, and promotes lung cancer cell apoptosis, through targeting c-Met and Bcl2. [score:8]
In the present study, we found that miR-206 was dramatically down-regulated in lung cancer tissues compared with matched normal lung tissues, and it inhibited the tumorigenic potential of lung cancer cells by down -regulating oncogenic targets, such as MET and Bcl2. [score:8]
To determine whether MET and BCL2 expression are indeed regulated by miR-206, the MET and BCL2 3′-UTR were cloned into a luciferase reporter plasmid (Fig. 4A), and the ability of miR-206 to inhibit expression of the adjacent hRluc coding region was quantified. [score:8]
Figure 5 A-B. miR-206 expression after transfected A549 and SK-MES-1 cells with miR-206 mimic, miR-206 mimic NC, miR-206 inhibitor or miR-206 inhibitor NC for twenty four hours. [score:7]
These results demonstrated miR-206 inhibited c-Met and Bcl2 expression in A549 cells, and loss of miR-206 would be attributed to the over -expression of c-Met and Bcl2 in lung cancer cells, which were the risks of NSCLS. [score:7]
Collectively, we discovered miR-206 targets 3′-UTR of c-Met and Bcl2 mRNA, and inhibits the expression of c-Met and Bcl2 in lung cancer cell lines (A549 and SK-MES-1). [score:7]
These results are in accordance with Liu's research, they also discovered over -expression of miR-206 decreased MMP-9, and increased p57 expression, which leading to inhibition of Hepatocellular carcinoma (HCC) HepG2 cells invasion and proliferation [27]. [score:7]
A-B. miR-206 expression after transfected A549 and SK-MES-1 cells with miR-206 mimic, miR-206 mimic NC, miR-206 inhibitor or miR-206 inhibitor NC for twenty four hours. [score:7]
Our study showed that exogenous miR-206 could down-regulate the expression of c-Met and Bcl2 protein and mRNA in lung cancer cells. [score:6]
Our study revealed that the over -expression of miR-206 is a associated with the up-regulation of p57 level in lung cancer cell (A549). [score:6]
Further, MiR-206 expression decreased in ERα -positive endometrial endometrioid adenocarcinoma (EEC) and its over -expression inhibited ERα -dependent proliferation, impaired invasiveness and induced cell cycle arrest in ERα -positive EEC cell lines [32]. [score:6]
Expression miR-206 is significantly down-regulated in primary human lung cancer. [score:6]
Kondo et al found that miR-206 is down-regulated in breast cancer and represses estrogen receptor alpha (ERα) expression [22]. [score:6]
Liu et al revealed that miR-206 over -expression inhibited the expression of Bcl2, but they did not further investigate the directed relationship between miR-206 and Bcl2. [score:6]
It has been reported that cyclin D1 is direct targets of miR-206 in 3T3-L1 cells [44] and HeLa cells [45], and over -expression of cyclin D1 promoted of breast cancer [44] and A549 [20] cells proliferation. [score:6]
These results suggest that miR-206 binds directly to the predicted binding site(s) in the BCL2 3′-UTR and negatively regulates BCL2 expression. [score:5]
However, when treated with miR-206 inhibitor, migration in miR-206 -expression defect A549 and SK-MES-1 cells were significantly increased by approximately 4 and 1.8 folds relative to blank A549 and SK-MES-1 cells (Fig. 7E-G, and K-M), respectively. [score:5]
F. s of A549 and SK-MES-1 cells after transfected with miR-206 mimic, miR-206 mimicNC, miR-206 inhibitor, miR-206 inhibitor NC. [score:5]
Our western blot results revealed that miR-206 inhibited the expression of c-Met (Fig. 5C and 5D) and Bcl2 (Fig. 5G and 5H) protein in A549 cells, which were confirmed by qRT-PCR of MET (Fig. 5E and 5F) and BCL2 (Fig. 5I and 5J) in A549 and SK-MES-1 cells. [score:5]
A. Shown are representative photomicrographs of A549 cells after transfected with miR-206 mimic, miR-206 mimic NC, miR-206 inhibitor ormiR-206 inhibitor NC for forty eight hours. [score:5]
Collectively, we discovered that miR-206 inhibits non-small cell lung cancer A549 ang SK-MES-1 cell growth, migration, invasion and colony formation, and promoted cell apoptosis by targeting 3′-UTR of c-Met and Bcl2. [score:5]
After transfection with miR-206 mimic, miR mimic NC, miR-206 inhibitor, miR inhibitor NC for forty eight hours, the BrdU (5-bromo-2-deoxyuridine; Sigma) stock solution at 10 mg/mL in saline was diluted 1000 × in the culture medium and incubated for 60 min. [score:5]
Moreover, we tested the caspase-3 activity after treatment of A549 and SK-MES-1 cells with miR-206 mimic or miR-206 mimic NC, miR-206 inhibitor or miR-206 inhibitor NC, and results showed that miR-206 significantly increased the caspase-3 activity in A549 and SK-MES-1 cell lysate, by approximately 12 and 8.9 folds increase than that of bank A549 and SK-MES-1 cells (Fig. 8E and 8F), respectively. [score:5]
In addition, miR-206 also inhibited CCND1 and CCND2 and increased p57 expression levels in lung cancer cells, which further contributed to the growth- delay efficacy of miR-206. [score:5]
However, when treated with miR-206 inhibitor, invasion in miR-206 -expression defect A549 and SK-MES-1 cells were significantly increased by approximately 5 and 2.3 folds relative to blank A549 and SK-MES-1 cells (Fig. 7H-J and N-P), separately. [score:5]
However, when treated A549 and SK-MES-1 cells with miR-206 inhibitor, the expression of c-Met (Fig. 5C and 5D) and Bcl2 (Fig. 5G and 5H) protein was remarkably increased in comparison with blank A549 cells, which was confirmed by qRT-PCR of MET (Fig. 5E and 5F) and BCL2 (Fig. 5I and 5J) in A549 and SK-MES-1 cells. [score:5]
Finally, ectopic expression of miR-206 in the lung cancer cell line (A549) significantly reduced cell growth, migration, invasion and colony formation, and promoted cell apoptosis, whereas depletion of miR-206 remarkably promoted lung cancer cell (A549) growth, migration, invasion and colony formation, and inhibited cell apoptosis. [score:5]
Figure 6 A. Shown are representative photomicrographs of A549 cells after transfected with miR-206 mimic, miR-206 mimic NC, miR-206 inhibitor ormiR-206 inhibitor NC for forty eight hours. [score:5]
The cells were washed with 1× PBS (pH7.4) and then transiently transfected with 50 nM miR-206 mimic or miR mimic NC, 100 nM miR-206 inhibitor or miR inhibitor NC, using Lipofectamine™ 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions. [score:5]
Moreover, the luciferase assay using a reporter containing the wild type miR-206 binding sequence at the 3′-UTR of c-Met and Bcl2 mRNA indicated that the luciferase activity could be significantly reduced or increased by over -expression or down-regulation of miR-206, which was in accordance with Yan's investigation that miR-206 targeted MET in Rhabdomyosarcoma. [score:5]
After overnight growth, cells were transfected with miR-206 mimic, miR mimic NC, miR-206 inhibitor and miR inhibitor NC for forty eight hours. [score:5]
As expected, invasion of miR-206 -expressing clones was inhibited by 65% in A549 and 47% in SK-MES-1 cells, relative to the blank A549 (Fig. 7H and 7I) and SK-MES-1 cells (Fig. 7N and 7O), respectively. [score:5]
Moreover, miR-206 also inhibited the expression of MMP-9, which was the key enzyme to promote tumor cell to invasion and migration. [score:5]
Further, our results of flow cytometric analysis demonstrated that forced expression of miR-206 resulted in a ∼40-fold increase in apoptotic cell death of A549 cell (Fig. 8H and 8I), while the percentage of apoptotic cells induced by miR-206 was decreased to the basal level when the cells were treated with the specific miR-206 inhibitor (Fig. 8H and 8I). [score:5]
Has-miRNA-206 mimic and mimic negative control, has-miRNA-206 inhibitor and inhibitor negative control were purchased from RiboBio Co. [score:5]
MiR-206 suppresses tumor growth in vivoTo confirm the tumor suppressor role of miR-206 in vivo, we established a BALB/c nude mouse xenograft mo del using A549 cells. [score:5]
Moreover, miR-206 suppresses luciferase activity by approximately 50% in A549 cells and 38% in SK-MES-1 cells when the reporter plasmid carried the wild type BCL2 3′-UTR (Fig. 4G and 4H), but no significant suppression was observed when the reporter plasmid carried a mutant BCL2 3′-UTR (i. e., pmiR-RB-REPORT [TM]-mut-BCL2–3′-UTR). [score:5]
These results suggest that miR-206 binds directly to the predicted binding site(s) in the MET 3′-UTR and negatively regulates MET expression. [score:5]
The down-regulation of MET could be a possible mechanism by which miR-206 regulates growth and metastatic potential of these cells. [score:5]
Moreover, expression of cyclin D1 protein (Fig. 5K and 5L) and mRNA of CCND1 (Fig. 5M and 5N), CCND2 (Fig. 5Q and 5R) and MMP-9 (Fig. 5O and 5P) were also negatively regulated by miR-206, while the pro-apoptosis gene of p57 (Fig. 5S and 5T) was positively regulated by miR-206, in A549 and SK-MES-1 cells. [score:5]
We showed that ectopic expression of miR-206 not only inhibited proliferation but also reduced cell migration and invasion motility of A549 cells. [score:5]
Then we examined the mechanism of miR-206 on lung cancer cell growth, and found that over -expression of miR-206 significantly inhibited A549 cell proliferation, while loss of miR-206 promoted cell growth in A549 cells. [score:5]
Ectopic expression of miR-206 suppresses tumor growth in vivo. [score:5]
The results show that miR-206 suppresses luciferase activity by approximately 40% in A549 cells and 32% in SK-MES-1 cells when the reporter plasmid carried the wild type MET 3′-UTR (Fig. 4D and 4E), but no significant suppression was observed when the reporter plasmid carried a mutant MET 3′-UTR (i. e., pmiR-RB-REPORT [TM]-mut-MET-3′-UTR). [score:5]
Ectopic expression of miR-206 inhibits proliferation and colony formation of A549 and SK-MES-1 cells. [score:5]
B and D. Shown are representative photomicrographs of BrdU staining after transfected A549 and SK-MES-1 cells with miR-206 mimic, miR-206 mimic NC, miR-206 inhibitor or miR-206 inhibitor NC for 24 h. Bar = 100 μm. [score:5]
MiR-206, which is highly expressed in human skeletal muscle, is down-regulated in many cancers. [score:5]
Figure 9Ectopic expression of miR-206 suppresses tumor growth in vivo A-B. Tumor volume and weight in nude mice. [score:5]
Moreover, Yan et al also found that loss of miR-206 could contribute to aberrant cell proliferation and migration, leading to rhabdomyosarcoma development by suppression of c-Met [28]. [score:4]
G. Shown are representative photomicrographs of colony formation assay after transfected withmiR-206 mimic, miR-206 mimic NC, miR-206 inhibitor or miR-206 inhibitor NC for ten days. [score:4]
Next, we examined miR-206 expression in NSCLS cell lines, and results demonstrated a lower expression of miR-206 in A549 and SK-MES-1 cell lines, compared with that of in normal lung cells HELF (Fig. 1B). [score:4]
To determine whether c-Met and Bcl2 expression are indeed regulated by miR-206 in vitro, we transfected NSCLS A549 and SK-MES-1 cells with miR-206 mimic and miR mimic NC. [score:4]
Zhang et al revealed that cyclin D2 is also a directive target of miR-206 in gastric cancer (SGC-7901 cells) [46]. [score:4]
Our data support the notion that the loss of miR-206 is associated with the up-regulation of MMP-9 level in lung cancer cells (A549 and SK-MES-1). [score:4]
Thus, it was concluded that the decreased expression of miR-206 might play an important role in lung cancer progression and development. [score:4]
Here, we reported that miR-206 is indeed suppressed in primary lung cancers compared with the matching normal tissues, and found 3′-UTR of the human MET and BCL2 mRNA are really targets of miR-206. [score:4]
Collectively, the aberration of miR-206 in A549 and SK-MES-1 cells will contribute to the down-regulation of the above key factors related to lung cancer (NSCLS). [score:4]
As expected, migration of miR-206 -expressing clones was inhibited by 55% in A549 and 45% in SK-MES-1 cells, compared with the blank A549 and SK-MES-1 cells (Fig. 7E-F and 7K and 7L), respectively. [score:4]
MET (hepatocyte growth factor receptor), which harbors two conserved miR-206 cognate sites, namely, 484–508 and 796–823 of MET 3′-UTR) (Fig. 4B and 4C), is a predicted target of miR-206. [score:3]
MiR-206 is down-regulated in primary human lung cancer. [score:3]
However, further studies showed miR-206 is expressed in other tissues and functioned as a potential anticancer role [21]. [score:3]
MiR-206 also promoted myogenic differentiation and block tumor growth in xenografted mice by down-regulation of Met tyrosine-kinase receptor, the product of the MET proto-oncogene [31]. [score:3]
To confirm the tumor suppressor role of miR-206 in vivo, we established a BALB/c nude mouse xenograft mo del using A549 cells. [score:3]
In contrast, miR-206 -expressing cells migrated toward the wound at a much slower rate (Fig. 7A-7D). [score:3]
To verify this result, we also did the, and results demonstrated that miR-206 over -expression significantly promoted A549 and SK-MES-1 cells vitality, while loss of miR-206 attenuated cell proliferation (Fig. 6F). [score:3]
Third, miR-206 can also suppress tumor growth in vivo. [score:3]
Yan et al also discovered miR-206 targets the 3′-UTR of c-Met, but they were in 499–505 and 814–820 of MET 3′-UTR [28]. [score:3]
First, miR-206 expression was significantly reduced in primary lung cancer. [score:3]
We further showed that decrease in miR-206 expression is associated with an increase in oncogene CCND1, CCND2 and MMP-9, and a decrease in p57. [score:3]
A549 and SK-MES-1 cells were grown in RPMI 1640 or DMEM medium containing 10% fetal bovine serum to ∼60% confluence and transfected with 50 nM miR-206 mimic or a negative control, 100 nM miR-206 inhibitor or a negative control. [score:3]
In our present study, we initially demonstrated that miR-206 promoted lung cancer cell (A549) death, by targeting 3′-UTR of BCL2, which encoded pro-survive protein Bcl2, and increased the casepase-3 activities. [score:3]
This result indicates that miR-206 significantly inhibits the tumorigenicity of A549 cells in the nude mouse xenograft mo del. [score:3]
In addition, BCL2 is also a predicted target of miR-206 on account of it harbors one conserved miR-206 cognate site, namely, 4034–4057 of BCL2 3′-UTR (Fig. 4F). [score:3]
Ectopic expression of miR-206 promotes apoptosis in A549 and SK-MES-1 cells. [score:3]
Hoechst 33342 staining revealed that miR-206 increased the number of apoptosis cells in A549 and SK-MES-1 cells, while inhibition of miR-206 attenuated DNA damaging and nuclear fragmentation (Fig. 8A-8D), separately. [score:3]
All these findings indicated that miR-206 may play a tumor suppressor role in various cancers. [score:3]
In addition, miR-206 suppresses tumor cell growth in vitro and tumorigenicity in vivo. [score:3]
Collectively, our experimental data may provide a strategy for targeting the miR-206/c-Met or miR-206/Bcl2 interaction in a novel therapeutic application to treat lung cancer patients. [score:3]
In summary, we have shown that miR-206 is dramatically down-regulated in human lung cancer tissues compared with normal lung tissues. [score:3]
The results showed that miR-206 expression in the tumors was significantly (p < 0.05) reduced in 13 lung cancers relative to their matched controls among 13 samples analyzed (Fig. 1A). [score:3]
All these studies further implicate a tumor suppressor role for miR-206. [score:3]
However, loss of miR-206 by transfecting with miR-206 inhibitor remarkably reduced the caspase-3 activity in A549 and SK-MES-1 cell lysate, by approximately 60% and 52% than that of bank A549 and SK-MES-1 cells (Fig. 8E and 8F), respectively. [score:3]
These results, taken together, clearly demonstrated that miR-206 expression markedly reduces the migration and invasion motility of lung cancer cells. [score:3]
MiRNA-206 is a skeletal muscle-enriched miRNA that inhibits proliferation of progenitor cells and promotes myogenesis [19, 20]. [score:3]
To further investigate the anticancer role of miR-206 in lung cancer, we transfected A549 and SK-MES-1 cells with miR-206 mimic or miR mimic NC, and miR-206 inhibitor or miR-206 inhibitor NC, separately. [score:3]
Further, miR-206 also suppresses tumor growth in vivo. [score:3]
We found that miR-206 significantly promoted apoptosis in A549 cells, while inhibition of miR-206 reversed the high level of apoptosis in comparison to miR-206 treated A549 cells (Figure 8G). [score:3]
MET and BCL2 proto-oncogene are targets of miR-206 at specific 3′-UTR site. [score:3]
B. The expression level of miR-206 in two NSCLS cell lines and normal HELF cells. [score:3]
In addition, our results of western-blot and qRT-PCR demonstrated that the decreased expression of c-Met and Bcl2 in tumors developed from miR-206-agomir -treated nude mice relative to control tumors (Fig. 9C and 9D). [score:3]
Ectopic expression of miR-206 in A549 and SK-MES-1 cells reduces cell migration and invasion motility. [score:3]
MiR-206 has also been shown to function as a pro-apoptotic factor in HeLa cells by targeting Notch3 signaling [24]. [score:2]
To determine whether miR-206 is down-regulated in lung cancer, we measured the mature miR-206 level in human primary lung tumors (NSCLS) and pair-matched lung tissues by qRT-PCR. [score:2]
MiR-206 suppresses tumor growth in vivo. [score:2]
For this purpose, the luciferase reporter plasmid pmiR-RB-REPORT [TM]-MET-3′-UTR or a mutant reporter plasmids carrying point mutations in the putative miR-206 binding sites was co -transfected with miR-206 mimics or miR mimic NC, separately. [score:2]
MiR-206 inhibits lung cancer cell migration and invasion. [score:2]
MiR-206 inhibits lung cancer cell proliferation and colony formation. [score:2]
These authors proposed that loss of miR-206 may be linked with breast cancer development. [score:2]
After 8 days, miR-206 agomir or miR agomir NC was directly injected into the implanted tumor every 4 days for seven times. [score:2]
However, miR-206 inhibitor treatment increased A549 and SK-MES-1 cell DNA synthesis by approximately 1.7 folds (Fig. 6B and 6C) and 1.6 folds (Fig. 6D and 6E) compared with blank A549 and SK-MES-1 cells, separately. [score:2]
Our results of BrdU staining revealed that miR-206 inhibited A549 and SK-MES-1 cell DNA synthesis by approximately 60% (Fig. 6B and 6C) and 50% (Fig. 6D and 6E), compared with blank A549 and SK-MES-1 cells, respectively. [score:2]
MiR-206 inhibits c-Met and Bcl2 in lung cancer cells. [score:2]
MiR-206 targets human MET and BCL2. [score:2]
Although Wang et al find in their study that miR-206 inhibits invasion and metastasis of lung cancer, they fail to investigate the potential mechanism [53]. [score:1]
A. miR-206 is significantly decreased in primary human lung cancer tissues in comparison to matched-normal lung cancer tissues. [score:1]
Next, we examined the role of miR-206 on A549 and SK-MES-1 cells apoptosis. [score:1]
F. The 3′-UTR of BCL2 harbors one miR-206 cognate site. [score:1]
The tumor volume and weight of mice treated with miR-206 agomir were significantly reduced relative to that of miR agomir NC (Fig. 9A and 9B). [score:1]
We used two different approaches to assess the role of miR-206 on the ability of A549 and SK-MES-1 cells migration. [score:1]
Then, we examined the role of miR-206 on A549 and SK-MES-1 cells migration and invasion. [score:1]
D-E. Relative luciferase activity of reporter plasmids carrying wild-type or mutant BCL2 3′-UTR in A549 and SK-MES-1 cells co -transfected with negative control (NC) or miR-206 mimic. [score:1]
These results demonstrated that miR-206 indeed promoted apoptosis in A549 cells. [score:1]
We then explored the underlying molecular mechanism of the antitumorigenic property of miR-206 in lung cancer cells. [score:1]
The present study also has shed light on the potential role of miR-206 on cancer metastasis. [score:1]
We first examined the role of miR-206 on A549 and SK-MES-1 cells proliferation. [score:1]
Figure 1 A. miR-206 is significantly decreased in primary human lung cancer tissues in comparison to matched-normal lung cancer tissues. [score:1]
A549 cells transfected with miR-206 mimic or negative control were trypsinized and resuspended in 1 × binding buffer at 1 × 10 [6] cells/mL. [score:1]
For the qRT-PCR detection of mature miR-206 expression, we purchased the Bulge-Loop™ miRNA qRT-PCR Primer Set and the miRNA qRT-PCR Control Primer Set (both from RiboBio). [score:1]
was conducted using One-way ANOVA Next, we examined the role of miR-206 on A549 and SK-MES-1 cells apoptosis. [score:1]
To our knowledge, this is the first report that reveals detail mechanism between loss of miR-206 and tumorigenic potential of lung cancer cells. [score:1]
G-H. Relative luciferase activity of reporter plasmids carrying wild-type or mutant BCL2 3′-UTR in A549 and SK-MES-1 cells co -transfected with negative control (NC) or miR-206 mimic. [score:1]
miR-206 agomir (miR-206) or miR agomir NC (NC) (RiboBio Co. [score:1]
B and C. The 3′-UTR of MET harbors two miR-206 cognate sites. [score:1]
[1 to 20 of 130 sentences]
2
[+] score: 362
Figure 7Western blotting analysis was performed to detect the protein expression of AKT, p-AKT, mTOR, p-mTOR in A. A549/DDP cells and A549 cells, B. miR-206 mimics transfected A549/DDP cells, C. MET shRNA transfected A549/DDP cells, D. MET inhibitors SU11274 treated A549/DDP cells, E. miR-206 inhibitors transfected A549 cells, F. MET overexpression vectors (ex-MET) transfected A549 cells, G. PI3K inhibitor LY294002 treated A549/DDP cells, H. mTOR inhibitor rapamycin treated A549/DDP cells. [score:13]
Western blotting analysis was performed to detect the protein expression of AKT, p-AKT, mTOR, p-mTOR in A. A549/DDP cells and A549 cells, B. miR-206 mimics transfected A549/DDP cells, C. MET shRNA transfected A549/DDP cells, D. MET inhibitors SU11274 treated A549/DDP cells, E. miR-206 inhibitors transfected A549 cells, F. MET overexpression vectors (ex-MET) transfected A549 cells, G. PI3K inhibitor LY294002 treated A549/DDP cells, H. mTOR inhibitor rapamycin treated A549/DDP cells. [score:13]
Taken together, our study demonstrated that miR-206 overexpression in human lung adenocarcinoma cisplatin resistant cells inhibited the EMT and cisplatin resistance by targeting MET and suppressing its downstream PI3K/AKT/mTOR signaling pathway. [score:9]
On the contrary, miR-206 inhibitors reduced E-cadherin expression, induced the expression of Vimentin, ZEB1 and Snail in A549 cells, while induced N-cadherin, Snail and ZEB1expression in H1299 cells (Figure 2F, Supplementary Figure 2G). [score:9]
FAM-labled mimic negative control (mimic NC), miR-206 mimics (mimics), inhibitor NC, miR-206 inhibitors, MET silence vectors p-GPU6-MET-shRNA (MET-shRNA), shRNA control, MET (Accession NO: NM_000245) overexpression vector pEZ/M98/neo-MET (ex-MET) and the ex-control were purchased from GenePharma (Shanghai, China). [score:7]
In contrast, miR-206 inhibitors and MET overexpression activated the PI3K/AKT/mTOR pathway and increased MDR1 expression in A549 cells. [score:7]
To determine whether the anti-EMT and anti-cisplatin resistance effects of miR-206 on DDP-resistant cells could be partly explained by its targeting of MET, we first analyzed how MET inhibitors, MET silence and MET overexpression affected EMT. [score:7]
To further support the role of PI3K/AKT/mTOR signaling in suppression of EMT and cisplatin resistance by miR-206, PI3K selective inhibitor LY294002 and mTOR inhibitor rapamycin was utilized in A549/DDP cells. [score:7]
Furthermore, western blotting showed that miR-206 mimics significantly decreased the expression of MDR1 in A549/DDP cells and H1299/DDP cells, while miR-206 inhibitors increased the expression of MDR1 in A549 cells and H1299 cells (Figure 2C, Supplementary Figure 2D). [score:7]
More importantly, we demonstrated that decreased miR-206 levels induced cisplatin resistance and EMT phenotype due to activation of MET/PI3K/AKT/mTOR axis, upregulation of MDR1, ZEB1 and Snail expression in DDP-resistant cells. [score:6]
miR-206 can inhibit the expression of VEGF and regulate the apoptosis and migration of laryngeal cancer cells [29]. [score:6]
These results provides a possible mechanism linking miR-206, MET/PI3K/AKT/ mTOR pathway, cisplatin resistance, by which downregulated expression of multi-drug resistance genes leads to cisplatin resistance in A549 cells. [score:6]
Overexpression of miR-206 or knockdown of its target MET reversed the mesenchymal features and sensitized DDP-resistant cells to cisplatin. [score:6]
Meanwhile, down-regulated miR-206 could increase MET expression level in A549 cells and H1299 cells (Figure 3C). [score:6]
These results indicate that miR-206 regulates MET protein in A549 cells by directly targeting MET 3′-UTR. [score:5]
Based on target prediction programs, we found that MET is a tentative target of miR-206. [score:5]
The cells were plated in 6-well plates (3×10 [5] cells/well) and 75 pmol of the miR-206 mimic or negative control were transfected into the A549/DDP cells, while a miR-206 inhibitors or inhibitor negative control were transfected into the A549 cells, using Lipofectamine-2000 (Invitrogen, USA) according to the manufacturer's instructions. [score:5]
These findings further confirmed the existence of an inverse correlation between the expression of miR-206 and MET expression in these cell lines. [score:5]
To determine whether miR-206 inhibits MET dependent PI3K/AKT/mTOR signaling pathways, we analyzed the effects of miR-206 or MET expression changes on PI3K/AKT/mTOR signaling. [score:5]
Low expression of miR-206 in lung adenocarcinoma tissues correlates with increased cisplatin resistance and MET expression. [score:5]
miR-206 suppresses breast cancer cell migration and invasion by targeting Cdc42 [28]. [score:5]
These results provide new insights into the molecular mechanisms of cisplatin resistance induced by decreased miR-206 levels in lung adenocarcinoma cells and suggest miR-206 and its target gene pathway could be novel therapeutic targets to reverse cisplatin resistance of lung adenocarcinoma cells. [score:5]
Furthermore, miR-206 mimics treatment caused the higher expression of E-cadherin and lower expression of mesenchymal markers including Vimentin, Snail and ZEB1 in A549/DDP cells. [score:5]
In contrast, miR-206 inhibitors or MET overexpression enhanced phosphorylation of AKT/ mTOR in A549 cells. [score:5]
Western blotting showed that miR-206 overexpression could significantly decrease MET expression in A549/DDP and H1299/DDP cells. [score:5]
In addition, our results in clinical lung cancer tissue samples show that the decreased expression of miR-206 closely correlated with increased MET expression and poor cisplatin sensitivity. [score:5]
We and others have demonstrated that miR-206 overexpression inhibited invasion and metastasis in lung cancer cells [26, 30]. [score:5]
Luciferase activity from a construct harboring miR-206 inhibitor sequence (PC group) was significantly decreased in A549 cells expressing either miR-206 or its negative control form. [score:5]
org, miRDB and TargetScan database), MET is a predicted target of miR-206 in humans. [score:5]
The results showed that both miR-206 mimics transfection and MET-shRNA treatment significantly decreased AKT, p-AKT, mTOR and p-mTOR protein levels in A549/DDP cells (Figure 7B-7C), and MET inhibitor SU11274 also resulted in a decrease in p-AKT, p-mTOR protein expression(Figure 7D). [score:5]
We and others have also reported miR-206 overexpression could inhibit invasion of lung cancers [22, 26, 30]. [score:5]
In contrast, miR-206 inhibitors and MET overexpression increased p-AKT, mTOR and p-mTOR protein levels in A549 cells (Figure 7E-7F). [score:5]
In the current study, we demonstrated that miR-206 could suppress EMT process and cisplatin resistance of lung adenocarcinoma cells, partly through targeting MET and its downstream PI3K/AKT/ mTOR pathway both in vitro and in vivo. [score:5]
In addition, invasion and migration assay further demonstrated that miR-206 mimics suppressed the invasion and migration of A549/DDP cells and H1299/DDP cells (Figure 2G, Supplementary Figure 3A-3B), whereas miR-206 inhibitors enhanced the invasion and migration of A549 cells and H1299 cells (Figure 2H, Supplementary Figure 3C-3D). [score:4]
In vitro drug sensitivity assayThe cells were plated in 6-well plates (3×10 [5] cells/well) and 75 pmol of the miR-206 mimic or negative control were transfected into the A549/DDP cells, while a miR-206 inhibitors or inhibitor negative control were transfected into the A549 cells, using Lipofectamine-2000 (Invitrogen, USA) according to the manufacturer's instructions. [score:4]
In this study, we found miR-206 was down-regulated in both A549/DDP cells and H1299/DDP cells. [score:4]
We demonstrated that decrease of EMT related transcription factors, such as ZEB1 and Snail expression is one of the molecular mechanisms from the deregulated miR-206 levels to the EMT. [score:4]
MET is a direct target of miR-206. [score:4]
To test whether the predicted miR-206 target site in the 3′-UTR of MET mRNA was responsible for its regulation, we cloned MET 3′-UTR wild type (MET-wt) or 3′-UTR mutant type (MET-mut) into downstream of the luciferase reporter gene and cotransfected with miR-206 mimics into A549 cells. [score:4]
In support of the role of miRNAs in cisplatin resistance and EMT in lung cancer, our study identified that miR-206 is down-regulated and could confer cisplatin resistance and EMT in A549/DDP cells and H1299/DDP cells. [score:4]
We further demonstrated that miR-206 directly target MET in lung cancer A549 cells. [score:4]
Recently, there has been increasing interest in understanding the role of miR-206 in cancer, and down-regulation of miR-206 has been observed in different types of cancers [21– 27]. [score:4]
To the best of our knowledge, we provided a first insight into the roles and possible mechanisms of miR-206 upregulation in chemosensitivity of A549 cells to cisplatin. [score:4]
miR-206 has been found to be down-regulated in many types of cancers including lung cancer [21- 27, 30]. [score:4]
C. A549/DDP cells were transfected with miR-206 mimics and A549 cells were transfected with miR-206 inhibotors for 48 h respectively. [score:3]
A. Expression levels of miR-206 and B. MET protein were detected in cisplatin “sensitive” (a, n =17) and “insensitive” (b, n = 17) lung adenocarcinoma tissues via qRT-PCR (normalized to U6 RNA) and immunostaining (Origninal magnification, ×100), respectively. [score:3]
miR-206 overexpression reverses cisplatin resistance, EMT, migration and invasion in DDP-resistant cells. [score:3]
Low expression of miR-206 and high levels of MET were strongly associated with the poor cisplatin sensitivity of lung adenocarcinoma patients. [score:3]
Here, we observed that miR-206 mimics transfection led to a change from elongated, fibroblastoid morphology to a rounded shap in both A549/DDP cells and H1299/DDP cells, whereas miR-206 inhibitors transfection resulted in an elongated fibroblast-like morphology of A549 cells and H1299 cells (Figure 2D, Supplementary Figure 2E). [score:3]
A luciferase reporter containing miR-206 inhibitor sequence was used as a positive control (PC). [score:3]
B. A549/DDP cells were transfected with miR-206 mimics, and A549 cells were transfected with miR-206 inhibitors. [score:3]
Both miR-206 mimics and MET-shRNA suppresses the phosphorylation of AKT/mTOR in A549/DDP cells. [score:3]
MET is involved in miR-206 inhibited EMT. [score:3]
Interestingly, we found that MET is also one of the targets of miR-206. [score:3]
Also, miR-206 mimics decreased the expression of N-cadherin, Vimentin, Snail and ZEB1 in H1299/DDP cells (Figure 2E, Supplementary Figure 2F). [score:3]
miR-206 inhibits EMT and cisplatin resistance via MET dependent PI3K/AKT /mTOR signaling pathways. [score:3]
MET is involved in miR-206 inhibited cisplatin resistance. [score:3]
In addition, miR-206 inhibitor sequence was also cloned into pmirGLO3 luciferase reporter vector as a positive control (PC). [score:3]
Therefore, these results further demonstrated in vivo that miR-206 inhibiting MET and its downstream PI3K/AKT/mTOR pathways is one potential mechanism to overcome cisplatin resistance in lung cancer. [score:3]
These data indicated the involvement PI3K/AKT/mTOR pathway in suppression of EMT and cisplatin resistance by miR-206. [score:3]
Decreased expression of miR-206 in gastric cancer is associated with tumor progression and poor survival [24]. [score:3]
Figure 4 A. Expression levels of miR-206 and B. MET protein were detected in cisplatin “sensitive” (a, n =17) and “insensitive” (b, n = 17) lung adenocarcinoma tissues via qRT-PCR (normalized to U6 RNA) and immunostaining (Origninal magnification, ×100), respectively. [score:3]
MET gene is a target of miR-206 in lung cancer cells. [score:3]
Despite MET has recently been identified as a target of miR-206 in rhabdomyosarcoma cells [44]. [score:3]
To further validate the role of miR-206 in cisplatin resistance, we transfected miR-206 mimics into A549/DDP cells and H1299/DDP cells, transfected miR-206 inhibitors into A549 cells and H1299 cells. [score:3]
C. The immunoreactivity of MET protein in cisplatin “sensitive” and “insensitive” tissues showed a statistically significant inverse correlation with the relative expression level of miR-206. [score:3]
Previous studies have reported that miR-206 could act as a tumor-suppressor in various cancers including lung cancer [21– 30]. [score:3]
As shown in Figure 4A, miR-206 was significantly down-regulated in the “insensitive” group tissues (n = 17) compared with that in the “sensitive” group (n = 17). [score:3]
We found that miR-206 inhibited the MET/AKT/ mTOR pathway and enhanced the A549/DDP cell sensitivity to cisplatin in vivo. [score:3]
Moreover, the stronger immunoreactivity of MET was significantly associated with lower miR-206 expression (r = 0.4086, P = 0.0165, Figure 4C), suggesting that miR-206-MET interaction might be biologically significant in cisplatin resistance. [score:3]
Therefore, activation of miR-206 or inactivation of its target gene pathway may be a potential strategy to reverse cisplatin resistance in human lung adenocarcinoma cisplatin resistant cells. [score:3]
PI3K/AKT/mTOR pathway is involved in miR-206/MET regulated cisplatin resistance, EMT, migration and invasion. [score:2]
miR-206/MET regulated PI3K/AKT/mTOR pathway. [score:2]
A. qRT-PCR assay showed a significant down-regulation of miR-206 in A549/DDP cells compared with in A549 cells. [score:2]
Furthermore, the expression of MET, AKT, p-AKT, mTOR and p-mTOR were significantly decreased in the miRNA-206 plus cisplatin group compared with DDP combined mimic NC group or DDP group. [score:2]
miR-206 agomirs and miR-206 agomir negative control (NC) (2 nmol; Genepharma, Shanghai, China) were given locally by direct injection into the xenografts every two days. [score:2]
MTT assay revealed that miR-206 mimics treatment led to significantly decreased resistance of A549/DDP cells and H1299/DDP cells to cisplatin, whereas miR-206 inhibitors transfection enhanced the resistance of A549 cells and H1299 cells to cisplatin (Figure 2B, Supplementary Figure 2B-2C). [score:2]
These data suggest that miR-206-MET play important roles in regulating EMT and cisplatin resistance in lung adenocarcinoma cells. [score:2]
Figure 2 A. qRT-PCR assay showed a significant down-regulation of miR-206 in A549/DDP cells compared with in A549 cells. [score:2]
A. Luciferase assay was performed in A549 cells that were cotransfected with miRNA mimics and reporter vectors carrying MET 3'UTR wild type (MET- wt), MET 3'UTR mutated type (MET- mut), and miR-206 inhibitor sequences (positive control) element. [score:2]
Our data provide a first insight into the function of miR-206 in regulating cisplatin resistance and EMT in cisplatin resistant lung adenocarcinoma cells. [score:2]
However, whether miR-206 is involved in regulating cisplatin resistance and EMT in human lung adenocarcinomas remains unclear. [score:2]
Figure 3 A. Luciferase assay was performed in A549 cells that were cotransfected with miRNA mimics and reporter vectors carrying MET 3'UTR wild type (MET- wt), MET 3'UTR mutated type (MET- mut), and miR-206 inhibitor sequences (positive control) element. [score:2]
These results further suggest that miR-206 and its downstream MET/AKT/mTOR pathway play important roles in controlling A549/DDP cells cisplatin sensitivity. [score:1]
To better understand the association between miR-206 and cisplatin resistance, a total of 34 clinical lung tumor tissue samples were collected from patients with advanced lung adenocarcinoma and divided into “sensitive” and “insensitive” groups according to the patient's response to cisplatin -based chemotherapy. [score:1]
MiR-206 is one of the most studied and best characterized miRNAs to date, which specifically expressed in skeletal muscle [20]. [score:1]
In the present study, we also assessed the anti-tumour effect of miR-206 in a cisplatin-resistant in vivo mice mo del. [score:1]
miR-206 decreased cisplatin resistance, EMT, migration and invasion of A549/DDP cells. [score:1]
To determine whether miR-206 plays a pivotal role in drug resistance in lung cancer cells, we measured the expression of miR-206 in the A549/DDP cells, H1299/DDP cells and their parental cells. [score:1]
miR-206 enhances A549/DDP cells to cisplatin sensitivity in vivo. [score:1]
These results indicated that miR-206 could reverses cisplatin resistance, EMT, migration and invasion of cisplatin resistant cells. [score:1]
In the present study, we found miR-206-MET axis regualted PI3K/AKT/mTOR pathway in lung cancer cells. [score:1]
[1 to 20 of 92 sentences]
3
[+] score: 295
However, at present it is not clear whether expression of miR-206/133b plays a functional role in Th17 lineage differentiation by targeting specific mRNAs or whether its expression may just be involved in epigenetic regulation of the Il17a/f locus. [score:8]
Therefore, we extended our analyses of miR-206/133b expression to CD4 [+] T cells positive or negative for RORγt expression as assessed by expression of a GFP reporter gene knocked into the Rorc locus [25]. [score:8]
Thus, CD27 expression might serve as an additional tool to assess the correlation between miR-206/133b expression and IL-17A expression. [score:7]
In addition to classical roles of miRNAs, namely gene-regulation by targeting 3′-UTRs of mRNA, it is thus conceivable that expression of the miRNAs miR-133b and miR-206 is involved in the regulation of Il17a and Il17f locus accessibility comparable to the involvement of miRNA in DNA methylation in plants [39]. [score:7]
Genome-wide expression analysis has revealed that neighboring genes are frequently co-expressed [17] suggesting that the miR-206/133b cluster and IL-17A/F might be co-expressed as well. [score:7]
In accordance with a less stringent correlation of CD27 expression and IL-17A expression, expression levels of miR-133b and miR-206 were only slightly elevated (2-fold and 2.5-fold, respectively) in CD27 -negative versus CD27 -positive γδ T cells (Fig. 3C, left panel). [score:7]
However, despite the high expression levels of miR-206/133b we found no detectable expression of Il17 in muscle tissue (Fig. S3) suggesting that the co-regulation of the miR-206/133b cluster and the Il17a/f locus is specific for T lymphocytes. [score:6]
Taken together, these data indicate that co -expression of miR-206/133b and IL-17A is not restricted to CD4 [+] Th17 cells, but also holds true for IL-17A expressing innate lymphocytes, suggesting that this co-regulation is a general phenomenon shared between αβ and γδ T cells. [score:6]
However, when comparing their expression in sorted activated/memory CD4 [+] T cells versus naive CD4 [+] T cells we found only a marginal upregulation of miR-206/133b in the former (<2 fold), which may reflect the few Th17 cells contained in the activated/memory CD4 [+] T cell population (Fig. S2). [score:6]
Here, we demonstrate elevated expression of miR-206/133b in in vitro polarized Th17 cells as well as in freshly isolated murine and human Th17 cells and in IL-17A producing innate lymphocytes such as CCR6 -expressing γδ T cells. [score:5]
We found that IL-23R expression was not required for miR-206/133b expression in IL-23R-reporter GFP [+] cells (Fig. 5). [score:5]
Taken together, our data reveal a previously unrecognized expression of miR-206/133b in lymphocytes, which is tightly coordinated with the expression of IL-17A. [score:5]
miRNAs miR-133b and miR-206 are syntenic to the Il17a/f locus and are specifically expressed in Th17 cells polarized in vitro Many miRNAs have been found to be clustered and are likely to be co-expressed when less than 50 kb apart [21]. [score:5]
Several targets of miR-133b and miR-206 such as DNA pol α, connexin43, histone deacetylase 4 (HDAC4) and the transcription factor Pitx3 have been reported to play a role in muscle development, regeneration of neuro-muscular synapses as well as osteoblast function [22], [42], [43], [44]. [score:4]
Nevertheless, both miR-133b and miR-206 expression was elevated 7-fold and 8-fold, respectively, in cells enriched for RORγt (GFP) expression when compared to RORγt (GFP) -negative cells (Fig. 2B left panel). [score:4]
IL-23/p19 induced activation of STAT3 leads to direct binding of phosphorylated STAT3 to IL-17A and IL-17F promoters suggesting that, in addition to chromatin remo deling, sharing of regulatory elements may as well contribute to co-regulation of miR-206/133b and IL-17A [45]. [score:4]
Likewise, the gene for two miRNAs miR-133b and miR-206, which are probably expressed from a bicistronic pri-miRNA [18], is located directly upstream of the Il17a and Il17f (Il17a/f) gene locus. [score:4]
So far, miR-206 and miR-133b have been reported to be specifically important for muscle regeneration and development [18], [19], [20] and their expression has been suggested to be largely restricted to skeletal muscle and osteoblasts. [score:4]
Figure S4 No regulation of the predicted target gene Ets1 by miR-133b or miR-206. [score:4]
In this work, we revealed a tight co-regulation of the expression of the miR-206/133b cluster with the potential to produce the pro-inflammatory cytokine IL-17A in lymphocytes. [score:4]
In fact, experiments, in which miR-206 or miR-133b or both were over-expressed in T cells showed no significant changes in the capacity of naive αβ T cells to become polarized towards Th17 or other Th lineages as well as iTreg. [score:3]
miRNAs miR-133b and miR-206 are syntenic to the Il17a/f locus and are specifically expressed in Th17 cells polarized in vitro. [score:3]
Correlation of IL-17A production and miR-206/133b expression in γδ T cells. [score:3]
Interestingly, the gene coding for the transcription factor Ets1 was predicted to be a target of both miR-133b (one predicted recognition site) and miR-206 (four predicted recognition sites). [score:3]
IL-17 producing in vivo polarized CD4 [+] Th17 cells express elevated amounts of miR-133b and miR-206. [score:3]
Expression levels of miR-133b (A) and miR-206 (B) were analyzed by qRT-PCR. [score:3]
Little impact of ectopic miR-206/133b expression on Th17 differentiation. [score:3]
Expression levels of miR-133b (D) and miR-206 (E) were analyzed by qRT-PCR. [score:3]
Therefore, we assessed miR-133b and miR-206 expression levels in freshly isolated T cells. [score:3]
0020171.g002 Figure 2IL-17 producing in vivo polarized CD4 [+] Th17 cells express elevated amounts of miR-133b and miR-206. [score:3]
Furthermore, we show that amongst multiple Th17 polarizing cytokines, IL-23 was the most important one for miR-133b and miR-206 expression. [score:3]
Functional outcome of ectopically expressed miR-133b and miR-206 in vitro and in vivo. [score:3]
Therefore, we isolated GFP -positive and GFP -negative γδ T cells from RORγt reporter mice as described for Figure 2B (Fig. 3B, right panels) and assessed the expression of miR-133b and miR-206. [score:3]
Figure S2 The activation status of CD4 [+] T cells and γδ T cells does not influence miR-133b and miR-206 expression. [score:3]
0020171.g007 Figure 7Functional outcome of ectopically expressed miR-133b and miR-206 in vitro and in vivo. [score:3]
Thus, of all cytokines tested IL-23 appears to be the most important for expression of miR-133b and miR-206 under standard conditions of in vitro polarization. [score:3]
Co -expression of IL-17A and miR-206/133b in γδ T cells. [score:3]
CD27 -positive and CD27 -negative γδ T cells were sorted from Tcrd-H2BeGFP reporter mice (Fig. 3C, right panels) and expression levels of miR-133b and miR-206 were assessed by qRT-PCR. [score:3]
Accordingly, miR-206/133b were initially described to be specifically expressed in skeletal muscle as well as osteoblasts suggesting that the Il17a/f locus might be accessible for gene transcription in these tissues as well. [score:3]
The Th17 polarizing cytokine IL-23 promotes expression of miR-206/133b as well as secretion of IL-17A. [score:3]
Similarly, elevated miR-206 expression (78-fold relative to Th0) was only detected in Th17, but not in Th1, Th2 or Treg polarized cells (Fig. 1E). [score:3]
Expression levels of miR-133b and miR-206 were analyzed by qRT-PCR. [score:3]
Since miR-133b and, especially, miR-206 are important for muscle cell proliferation and differentiation [24], we sought to exclude the possibility that cell activation and proliferation correlated with heightened expression of these miRNAs. [score:3]
IL-23 promotes expression of miR-206/133b. [score:3]
Figure S1 Mitogenic stimulation of in vitro Th17 polarized cells does not change the expression level of miR-133b or miR-206. [score:3]
0020171.g003 Figure 3(A) γδ T cells from Tcrd-H2BeGFP mice were sorted into a CCR6 [+] and CCR6 [−] populations and analyzed for expression of miR-133b and miR-206 by qRT-PCR. [score:3]
Th17 cells express elevated amounts of miR-133b and miR-206 in vivo. [score:3]
miRNAs miR-133b and miR-206 are syntenic to the IL-17A/IL-17F locus and are specifically expressed in Th17 cells polarized in vitro. [score:3]
Expression of miR-133b and miR-206 was assessed using qRT-PCR. [score:3]
However, we could not confirm an effect of miR-133b or miR-206 overexpression on constructs containing the 3′-UTR of the Ets1 gene in the context of the BW5147α-β- thymoma cell line (Fig. S4). [score:3]
Indeed, a very recent comprehensive resource study based on deep-sequencing reproduced our findings that miR-206/133b are specifically upregulated in Th17 cells compared to other T cell subsets [40]. [score:3]
It was thus instrumental to test whether co -expression of miR-133b and miR-206 is restricted to CD4 [+] Th17 cells or whether it is a more general phenomenon. [score:3]
Notably, miR-206 was expressed to considerable extents in Th17 cells with more than 1000 sequence tags per million. [score:3]
Primary human Th17 cells, but not Th1 cells, express miR-133b and miR-206. [score:3]
This is consistent with the observation that combination of all four cytokines generally used for Th17 polarization, namely IL-23, TGF-β, IL-6 and IL-1β or the additional use of IL-21 and TNF-α resulted in a profound synergistic effect with respect to miR-133b and miR-206 upregulation when compared to IL-23 alone or a combination of two cytokines (Fig. 4A, B). [score:3]
Th17 cells express elevated amounts of miR-133b and miR-206 in vivo Although in vitro polarization recapitulates the phenotypes of various Th lineages, in vitro and in vivo polarized cells may not necessarily be identical. [score:3]
Thus, in CD4 [+] T cells miR-133b and miR-206 are co-expressed with IL-17A in vivo. [score:3]
However, additional stimulation of Th17-polarized cells with PMA/ionomycin did not influence the expression of miR-133b and miR-206 (Fig. S1). [score:3]
0020171.g001 Figure 1miRNAs miR-133b and miR-206 are syntenic to the IL-17A/IL-17F locus and are specifically expressed in Th17 cells polarized in vitro. [score:3]
Similarly, over -expression of miR-206 or miR-133b in bone marrow chimeras did not reveal striking changes in the frequency of IL-17 producing CD4 [+] Th or CD4 [−] cells. [score:3]
P-value for miR-206 in IL-17A [+] compared to IFN-γ [+] expressing cells was 0.0645. [score:2]
Together, these results indicate that the two miRNAs of the miR-206/133b cluster are indeed co-regulated together and with the neighboring IL-17 locus. [score:2]
Consistent with data obtained from in vitro polarized cells, IL-17A secreting cells expressed 16-fold higher levels of miR-133b and 26-fold higher levels of miR-206 when compared to IL-17A negative CD4 [+] T cells (Fig. 2A, left panel). [score:2]
In conclusion, we provide evidence that the two miRNAs of the miR-206/133b cluster neighboring the Il17a/f locus are co-regulated in murine and human lymphocytes. [score:2]
Using quantitative Real-Time PCR (qRT-PCR), we found considerable differences of miR-206/133b expression levels between IL-17 producing and non-producing cells suggesting high specificity of the assay. [score:2]
Synteny of the miR-206/133b and Il17a/f loci is conserved among mammals and chicken, suggesting that the transcriptional co-regulation is physiologically relevant. [score:2]
qRT-PCR revealed that CCR6 -positive γδ T cells expressed 15-fold and 21-fold higher levels of miR-133b and miR-206, respectively, when compared to CCR6 -negative γδ T cells (Fig. 3A, left panel). [score:2]
We found that in the murine genome the miR-206/133b cluster lies in close proximity (less than 50 kb upstream) to the genes coding for the cytokines IL-17A and IL-17F (Fig. 1A), which themselves are organized syntenically in a head-to-head direction and probably arose through gene duplication. [score:2]
Expression levels for miR-133b and miR-206 were compared by qRT-PCR relative to Th0 (control). [score:2]
KI mice were compared for their miR-133b and miR-206 expression in (C) and (D). [score:2]
In order to clarify the role of IL-23 for the induction of miR-206/133b in vivo we sorted αβ or γδ T cells from either heterozygous or homozygous IL-23R-GFP knock-out/reporter-knock-in mice [30]. [score:2]
The validity of the qRT-PCR assays for miR-133b and miR-206 was assessed by overexpression and subsequent detection of these in BWα [−]β [−] cells (Fig. S5). [score:2]
Furthermore, miR-206/133b are close to a conserved noncoding sequence (CNS-1 or -60 region), which was recently reported to undergo chromatin remo deling in Th17 cell differentiation and therefore possibly provides accessibility to regulatory elements [38]. [score:2]
Taken together, we discovered co-regulation of miR-133b and miR-206 with the Il17a/f locus as a novel feature of T cell differentiation that is shared between mouse αβ and γδ T cells and also extended to human Th17 cells. [score:2]
KI mice were compared for their miR-133b and miR-206 expression in (A) and (B). [score:2]
Furthermore, to test a potential role of miR-133b and miR-206 in the development of IL-17 producing cells in vivo, we retrovirally transduced bone marrow derived hematopoietic precursors and generated bone marrow chimeras that contained transduced GFP [+] and non-transduced GFP [−] T cells. [score:2]
Although a certain degree of donor variability was observed, expression levels of miR-133b and miR-206 were consistently higher in IL-17A secreting human T cells (2 to 4-fold and 15 to 60-fold, respectively) when compared to Th0 cells (Fig. 6). [score:2]
Taken together, these results point to an important role of IL-23 signaling in miR-206/133b induction in lymphocytes and strengthen the hypothesis of a strict co-regulation of miR-206/133b and IL-17A. [score:2]
Thus, our data indicate that the miR-206/133b cluster is co-regulated with IL-17 in human T cells as well. [score:2]
However, the extent of IL-17 induction by individual cytokines may vary and thus comparing induction of IL-17 with induction of miR-206/133b by individual Th17 polarizing cytokines might provide some mechanistic insight into miR-206/133b/IL-17 co-regulation. [score:2]
Given these apparent differences, we tested whether miR-206/133b and IL-17 were co-regulated in human Th17 cells as well. [score:2]
miR-133b and miR-206 form such a cluster with a distance of approximately 4 kb between the coding sequences of the two mature miRNAs. [score:1]
To this end, we employed retroviral vectors for miRNAs miR-133b and miR-206 based on MDH1-PGK-GFP_2.0 [35]. [score:1]
IL-23R signalling is not essential for the induction of miR-133b and mir-206. [score:1]
Both miR-133b induction (Fig. 4D) as well as miR-206 induction (Fig. 4E) correlated strongly with secretion of IL-17A with correlation coefficients R [2] of 0.97 and 0.95, respectively. [score:1]
The retroviral constructs encoding mmu-miR-133b and mmu-miR-206 were generated by inserting the respective pre-miRNA sequences flanked by approximately 125 bp into the 3′LTR of the vector MDH-PGK1-GFP_2.0 (Addgene, [35]). [score:1]
By nucleofection with the Amaxa-nucleofection reagent the psiCHECK-2-Ets1 vector was introduced into the BW5147 α-β- cell line that was stably transduced with either the empty MDH1-PGK-GFP2.0 (Addgene) plasmid, the latter plasmid with miR-133b or with miR-206. [score:1]
Performing whole genome alignment using VISTA [23] we tested whether the proximity of miR-206/133b to the Il17a/f locus is similarly conserved. [score:1]
This qualifies transcription of miR-133b and miR-206 as a novel marker for T cells of an IL-17-producing phenotype. [score:1]
Finally, to examine a potential functional role of the miR-206/133b cluster in Th17 polarization, we undertook a series of efforts to manipulate the expression of the two investigated miRNAs in T cells both in vivo and in vitro. [score:1]
Notably, under these conditions, addition of IL-23 alone was able to induce low levels of miR-133b and miR-206 (Fig. 4A, B) as well as IL-17A as assessed by (Fig. 4C). [score:1]
The two miRNAs miR-133b and miR-206 are located in close proximity upstream to the Il17a/f locus. [score:1]
Location of miR-206/133b within the reported locus control region of the Il17a/f gene is consistent with this hypothesis. [score:1]
Proc Natl Acad Sci U S A 43 Kim HK Lee YS Sivaprasad U Malhotra A Dutta A 2006 Muscle-specific microRNA miR-206 promotes muscle differentiation. [score:1]
In order to more quantitatively assess the correlation between induction of miR-133b and miR-206 versus secretion of IL-17A dependent on the different cytokine cocktails used for polarization, we determined the respective correlation coefficients. [score:1]
In contrast, miR-206/133b levels were largely identical between human Th1 and Th0 cells. [score:1]
In this study we found that both miR-206/133b and IL-17A can be induced by IL-23 signaling. [score:1]
The miR-206/133b cluster is present in all vertebrate genomes analyzed so far [22]. [score:1]
Although statistically not significant, we observed a trend pointing to a higher frequency of IL-17 producing cells among the CD4 [+] Th and CD4 [−] cells in chimeras from bone marrow transduced with either miR-133b or miR-206 but not the empty vector (Fig. 7B, C). [score:1]
Lineage negative bone marrow was transduced with miR-133b or miR-206 or with the empty vector MDH1-PGK-GFP2.0 and served to reconstitute lethally irradiated C57BL/6 wild type mice. [score:1]
Transcriptional activity of the miR-206/133b cluster may promote opening of the whole region including the Il17a/f locus. [score:1]
This analysis revealed that indeed miR-206/133b is syntenic to the Il17a/f locus in mouse and humans (Fig. 1B) as well as in rat and chimpanzee (data not shown). [score:1]
Furthermore, the mature miRNA sequences of miR-133b and miR-206 are identical between mouse, human, rat and chimpanzee (Fig. 1C). [score:1]
11.10 mice were retrovirally transduced with miR-133b or miR-206 or with both and stimulated under Th17 polarization inducing conditions. [score:1]
[1 to 20 of 104 sentences]
4
[+] score: 242
Overexpression of miR-206 in HeLA cancer cells increases apoptosis by inhibiting Notch3 protein expression [13] and such over- expression plays a major role in PAH [14], [15]. [score:9]
hPASMCs that over-expressed miR-206 showed higher α-SM actin and calponin mRNA expression (Figure 5A) and protein (Figure 5B and supplementary figure S1A&B) levels compared to controls, while those expressing antimiR-206 have decreased expression levels of these same proteins. [score:8]
A significant increase in the expression of smooth muscle phenotypic markers, α -SMA and calponin, was observed in cells over -expressing miR-206 also induces differential expression. [score:7]
Since miR-206 is known to target Notch3 expression in breast cancer, Notch3 expression levels in miR-206 transfected cells were assessed via immuno-blotting. [score:7]
miR-206 increases apoptosis and inhibits tumor formation [13] in cancer cells by directly targeting Notch3. [score:6]
These results indicate that over -expression of miR-206 can increase apoptotic activity in hPASMCs and its down-regulation reduced apoptosis of hPASMCs. [score:6]
C) Real time PCR analysis for proliferation marker PCNA indicates decrease expression of proliferation markers in cells transfected with miR-206 and increased expression of proliferation markers in cells transfected with antimiR-206. [score:5]
These results indicate that miR-206 inhibits Notch3 expression in hPASMCs. [score:5]
Our in-vitro studies using hPASMCs show that over -expressing miR-206 decreases proliferation and increases apoptosis while reducing levels of miR-206 has opposing effects, indicating that reduced expression levels of miR-206 may be contributing to the observed hyper-proliferative state of hPASMCs in PAH. [score:5]
miR-206 reduces Notch-3 expression and rescues the proliferative phenotype by inhibiton of Notch 3 in hPASMCs. [score:5]
miR-206 Inhibits Expression of Notch3 in hPASMCs. [score:5]
miR-206 also inhibits Notch3 protein expression levels and providing an explanation for increased Notch-3 levels in PAH. [score:5]
We report for the first time that over expression of miR-206 decreases proliferation, increases apoptosis and induces smooth muscle cell differentiation markers (α-SMA and calponin) expression in human PASMCs. [score:5]
Notch-3 expression levels were assessed in hPASMCs transfected with miR-206, antimiR-206 and control miR A) A representative western blot is shown wherein miR-206 transfected cells show decreased expression of notch-3 compared to controls while antimi-206 treated samples show a higher expression of Notch3 compared to controls. [score:5]
0046808.g006 Figure 6 Notch-3 expression levels were assessed in hPASMCs transfected with miR-206, antimiR-206 and control miR A) A representative western blot is shown wherein miR-206 transfected cells show decreased expression of notch-3 compared to controls while antimi-206 treated samples show a higher expression of Notch3 compared to controls. [score:5]
As demonstrated in the study, expression of miR-206 down regulates Notch3 levels in hPASMCs, and when miR-206 is abrogated by using anti miR-206, Notch3 expression increases compared to controls. [score:5]
MiR-206 transfected cells show increased expression of SMC markers α-SMA and calponin compared to controls, while antimiR-206 transfected cells show reduced expression of SMC markers. [score:4]
miR-206 is increases expression of SMC differentiation markers, SMA and calponin and suggest that it may also play a crucial role in regulating SMC differentiation. [score:4]
Proliferation was significantly suppressed in miR-206 over expressed PASMC’s isolated from mice exposed to hypoxia when compared to control transfected mice PASMCs (Figure 7A). [score:4]
Overexpression of miR-206 significantly decreased smooth muscle cell proliferation by 37%, while inhibition of miR-206 by antimiR-206 significantly increased proliferation by 15% compared to controls (Figure 2B). [score:4]
These results suggest that miR-206 is a potent regulator of PASMCs and a disturbance in its expression levels can lead to PAH. [score:4]
hPASMCs that over expressed miR-206 were found to have lower Notch3 protein levels as compared to controls, while those transfected with antimiR-206 had increased expression levels of this protein (Figure 6A and supplementary figure S2). [score:4]
miR-206 Over Expression Induces hPASMCs Differentiation Markers. [score:3]
miR-206 targets the receptor protein, Notch3, found to play a role in tumorogenesis [13]. [score:3]
miR-206 is significantly down-regulated in hypoxic PAH mice compared to controls as illustrated in this study. [score:3]
A significant down regulation in the expression of miR-206 in hypoxic PAH mice compared to controls was observed. [score:3]
These results suggest that miR-206 over expression decreased proliferation, migration, contraction and increased apoptosis in PASMC’s of hypoxia induced PAH mice. [score:3]
miR-206 Expression Level in Mouse PASMCs. [score:3]
These results indicate that over -expression of miR-206 decreases cellular migration in hPASMCs. [score:3]
miR-206 increases expression of SMC markers. [score:3]
Regulation of Notch3 by miR-206 suggests that miR-206 could be used as a potential therapeutic molecule to modulate Notch3 functions, which promotes PAH development. [score:3]
miR-206 Over Expression Decreases Proliferation in hPASMCs. [score:3]
Percentage collagen lattice area was assessed in miR-206 overexpressed PASMCs isolated from hypoxia exposed mice. [score:3]
Expression of SMC differentiation markers α-smooth muscle actin (SMA) and calponin was analyzed in hPASMCs transfected with miR-206, antimiR-206 and controls by A) Real time PCR and B) Western blotting. [score:3]
The findings as demonstrated in this study, over -expression of miR-206 reduces proliferation and increases apoptosis of hPASMCs are consistent with these known functions of Notch3. [score:3]
miR-206 Over Expression Decreased Proliferation, Migration, Contraction and Increased Apoptosis in PASMC’s of Hypoxia Induced PAH Mice. [score:3]
PASMCs were isolated to assess the functional effects of over expression of miR-206 on proliferation, migration, contraction and apoptosis. [score:3]
miR-206 expression levels were found to be significantly lower in mice with pulmonary hypertension induced by hypoxia as compared to normoxic mice and suggest that miR-206 may play a role in regulating the proliferative phenotype of the pulmonary vasculature. [score:3]
These results support the hypothesis that miR-206 expression decreases proliferation in hPASMCs. [score:3]
miR-206 Overexpression Increases Apoptosis in hPASMCs. [score:3]
0046808.g005 Figure 5 Expression of SMC differentiation markers α-smooth muscle actin (SMA) and calponin was analyzed in hPASMCs transfected with miR-206, antimiR-206 and controls by A) Real time PCR and B) Western blotting. [score:3]
There was a 2.5-fold increased percentage of apoptotic cells in hPASMCs over -expressing miR-206. [score:3]
hPASMCs were transfected with negative control, miR-206 or anti miR-206 over expressing plasmids and Caspase 3 activity was assessed as per the manufacturer instructions. [score:3]
Suppressed levels of miR-206 observed in PAH mice might facilitate the proliferation and migration of PASMCs and enhance their resistance to apoptosis, leading to the thickening of the medial layer of pulmonary artery. [score:3]
miR-206 Over Expression Decreases Cellular Migration in hPASMCs. [score:3]
miR-206 down regulates proliferation of human PASMCs. [score:2]
A significantly (p<0.05) decreased expression levels of miR-206 was observed in PASMCs of hypoxia induced PAH mice compared to controls (Figure 1B). [score:2]
B) Rescue experiments were performed using hPASMCs transfected with miR-206 and Notch 3 over expressing plasmids or both and proliferation was assessed using 96 cell proliferation assay kit. [score:2]
miR-206 is Down regulated in Hypoxia induced PAH mice. [score:2]
In vivo experiments showed lower expression of miR-206 in hypoxia induced PAH mice when compared to control mice (Room air). [score:2]
Cells over -expressing miR-206 were found to migrate towards the center of the wound at a lower rate as compared to the controls, which almost completely enclose the wound field after 24 hours (Figure 4A). [score:2]
Apoptosis was significantly increased in miR-206 over expressed PASMCs isolated from hypoxia exposed mice (Figure 7B) compared to control transfected PASMCs (PAH+miR-206). [score:2]
miR-206 is down- regulated in many forms of cancers [11], [12]. [score:2]
Our data shows a significant increase in Casapase 3 activity in miR-206 over expressing hPASMCs compared to controls. [score:2]
Migration was significantly decreased in PASMCs over expressing miR-206 compared to control vector transfected cells (Figure 7D). [score:2]
This suggests that miR-206 may be an important regulator in the differentiation of hPASMCs. [score:2]
In conclusion, miR-206 appears to be a key regulator of the PASMCs function in the pulmonary vasculature. [score:2]
Therefore, a biological explanation for an increase in Notch3 levels in PASMCs in PAH by down regulating miR-206 is provided for the first time. [score:2]
miRs are known to regulate many genes, and it is possible that effect of miR206 on increased proliferation and reduced apoptosis could be because of its effect on other proliferation associated genes such as VEGF or cyclin D2, as reported earlier [32]. [score:2]
The effects of mir-206 on the SMC phenotype could be attributed, at least in part, to its effect on Notch3, a known factor that represses SMC differentiation and involved in the pathogenesis of PAH development [28], [34]. [score:2]
miR-206 Levels are Down Regulated in Hypoxia Induced PAH Mice. [score:2]
Therefore, relative expression levels of hPASMCs phenotypic markers were assessed to measure the effect of miR-206 on hPASMCs differentiation. [score:1]
C) Caspase 3 activity in hPASMCs transfected with miR-206, anti miR-206 or negative control. [score:1]
miR-206 has been studied in various cancer cells [12], [13], [22], however, miR-206 has not been studied in PAH hPASMCs. [score:1]
C) Migration of hPASMCs transfected with miR-206, antimiR-206, and control miR represented as % migration. [score:1]
This data suggests that, miR-206 rescues Notch3 mediated proliferative effects in hPASMCs. [score:1]
To determine the functional role of miR-206, hPASMCs were transfected with a miR negative control, miR-206 plasmid vector, or antimiR-206 and the levels of miR-206 was analyzed using q PCR (Figure 2A). [score:1]
Further to assess miR-206 mediated regulation of Notch 3, we performed rescue experiments where in, hPASMCs were transfected with either miR-206 or Notch 3 or both and post transfection, we performed proliferation assay. [score:1]
miR-206 increases apoptosis in hPASMCs. [score:1]
There were no significant differences in the number of migrating cells between the anti miR-206 samples and the controls. [score:1]
Additionally, we analyzed the functional effects of miR-206 on migration using a kit as per the manufacturer instructions (Figure 4C). [score:1]
We investigated the effects of miR-206 over expression on apoptosis in hPASMCs by TUNEL staining. [score:1]
miR-206 treated samples showed increased numbers of TUNEL positive cells 24 hours after transfection, indicating increased apoptotic activity (Figure 3A). [score:1]
miR-206 decreases migration of hPASMCs. [score:1]
PASMCs isolated from mice exposed to hypoxia were transfected with control vector or miR-206 or anti-miR 206 and were re suspended in collagen matrix gel. [score:1]
hPASMCs transfected with anti miR-206 showed decreased apoptosis (Figure 3C). [score:1]
0046808.g007 Figure 7 PASMCs were isolated from mice exposed to hypoxia and functional effects of miR-206 on proliferation, apoptosis, contraction and migration were analyzed post transfection. [score:1]
miR-206 plasmid was purchased from Addgene (Cambridge, MA. [score:1]
These results indicate that miR-206 plays a role in differentiating hPASMCs. [score:1]
Quantitatively, there was a significant decrease in the number of cells that migrated towards the interior of the initial wound field at 24 hours in miR-206 transfected hPASMCs (Figure 4B). [score:1]
hPASMCs and mouse PASMCs were transfected with 500 ng of miR-206 or 10 pm of antimiR-206 or negative control miR using a Primary P1 Nucleofection Kit and 4D Nucleofector machine (Lonza, GA). [score:1]
These reduced miR-206 levels could also contribute to the observed increased Notch3 levels in PAH. [score:1]
miR-206 decreases proliferation, migration, contraction and increases apoptosis in PASMC’s of hypoxia induced PAH mice. [score:1]
PASMCs were isolated from mice exposed to hypoxia and functional effects of miR-206 on proliferation, apoptosis, contraction and migration were analyzed post transfection. [score:1]
miR-206 induces differentiation of myoblasts [33]. [score:1]
[1 to 20 of 85 sentences]
5
[+] score: 233
Other miRNAs from this paper: hsa-mir-21
miR-206 suppresses the translation of the tumor-suppressor PDCD4 and promotes tumor cell survivalWe previously reported that RAS-ERK signaling, a prosurvival pathway, is maintained in TNBC cells by KLF4, in part through its regulation of miR-206. [score:8]
36, 37 Although on its own each miR exerts only subtle influences on RAS-ERK pathway activity, the coexpression of miR-206 and miR-21 potently represses the expression of pathway inhibitors including RASA1 and SPRED1. [score:7]
miR-206 suppresses the translation of the tumor-suppressor PDCD4 and promotes tumor cell survival. [score:7]
The tumor-suppressor PDCD4 was identified as a potential miR-206 targeted transcript by multiple miR-target prediction tools. [score:7]
In addition, the level of KLF4 was suppressed, attributed to direct regulation of KLF4 protein translation by miR-206 (Figure 3c, left lower panel). [score:7]
miR-206 promotes cell survival by suppressing CX43 in MaCSCsOur identification of miR-206 regulation of PDCD4 led us to seek additional targets of this miR that may be important for promoting cell survival. [score:6]
As shown by anti-miR treatment of TNBC cells, endogenous miR-206 directly repressed the translation of the tumor suppressors PDCD4 and CX43 and promoted tumor cell survival, chemoresistance and in vivo tumor initiation. [score:6]
Similarly, inhibition of miR-206 led to elevated CX43 levels, and transfection of miR-206 mimic was suppressive (Figure 6a, middle and right panels). [score:5]
45, 80, 81, 82, 83 These tumor-suppressor-like effects of miR-206 may result from higher level enforced expression of the exogenous miR. [score:5]
In TNBC cells, the activity of a translational reporter containing the CX43 3' UTR was induced by 1.5-fold following anti-miR-206 treatment, and suppressed by 53% following transfection of miR-206 mimic (Figures 6b and c). [score:5]
Supporting the direct regulation of CX43 by miR-206 in breast tumor cells, mutation of site A (mut206-A) abolished regulation by miR-206 (Figure 6c). [score:5]
Multiple previous studies have reported that enforced expression of miR-206 can suppress tumor cell proliferation, invasion or metastasis. [score:5]
[35] We previously identified microRNAs, including microRNA-206 (miR-206) and miR-21, as direct transcriptional targets of KLF4 that promote RAS-extracellular signal-regulated kinase (ERK) signaling in triple -negative breast cancer (TNBC) cells. [score:5]
Similarly as observed for KLF4, transient inhibition of endogenous miR-206 by anti-miR-206 transfection suppressed tumor initiation in vivo but did not alter the in vitro proliferation or the MaCSC abundance. [score:5]
Reporter regulation by miR-206 was abolished by mutation of site WT-A, but not by mutation of site WT-B, thus identifying site WT-A as a functional miR-206 -binding site (Figure 5b and c). [score:4]
Consistent with previous studies, miR-206 was suppressed following KLF4 knockdown (Figure 3a, left lower panel). [score:4]
44, 45, 47, 48, 49 In agreement with previous studies, we observed that miR-206 is upregulated in human breast cancers that display a higher grade, in human TNBCs and in basal-like mammary tumors derived from the C3(1)/ TAg GEMM (Figure 1a and c). [score:4]
Furthermore, miR-206 directly represses KLF4 translation, constituting a feedback loop. [score:4]
Our identification of miR-206 regulation of PDCD4 led us to seek additional targets of this miR that may be important for promoting cell survival. [score:4]
Direct regulation of PDCD4 by miR-206 was determined using translational reporter assays. [score:4]
Consistent with regulation of PDCD4 by miR-206, KLF4 depletion in MDA-MB-231 cells increased PDCD4 expression (Figure 5a, left panel). [score:4]
[60] Among the targeted gap junction proteins, CX43 is a validated miR-206-regulated transcript, as previously shown in muscle cells. [score:4]
In this study, suppression of endogenous miR-206 blocked tumor initiation, and moderate (fivefold) overexpression of exogenous miR-206 promoted initiation in a limiting dilution assay. [score:4]
miR-206 was upregulated in three of these four cases. [score:4]
The following anti-miR inhibitors (AM) and miR -mimics (PM) were obtained from Ambion and diluted to 20 μ M in nuclease-free water: hsa-miR-206 (AM10409, PM10409), AM -negative control (AM17010), and PM -negative control (AM17110). [score:3]
miR-206 promotes cell survival by suppressing CX43 in MaCSCs. [score:3]
Furthermore, inhibition of the endogenous miR-206 moderately sensitized TNBC cells to either agent (Figure 7b). [score:3]
We identified the tumor-suppressor programmed cell death 4 (PDCD4) as a potential mediator of cell survival by miR-206. [score:3]
Mirroring the role of endogenous miR-206, depletion of each tumor suppressor did not alter the abundance of CSCs, but instead enhanced tumor cell survival consistent with previous reports. [score:3]
Supporting functional roles downstream of KLF4 and miR-206, suppression of either PDCD4 or CX43 led to anoikis resistance, an intrinsic property of CSCs. [score:3]
75, 76, 77, 78, 79 In a mammary cancer context, miR-206 expression is elevated in ER [-] tumors, which are enriched for MaCSCs. [score:3]
Prosurvival signaling by miR-206 was attributed to direct regulation of PDCD4 and CX43, and miR-206 enhanced the chemoresistance of TNBC cells. [score:3]
Consequently, KLF4 and/or miR-206 may be therapeutically targeted to selectively cripple MaCSCs in TNBCs. [score:3]
Compared with normal mammary tissues or tumors arising in the luminal MMTV_ Neu mo del, [46] we observed upregulation of both KLF4 and miR-206 in basal-like tumors derived from the C3(1)/ SV40 large T antigen (C3(1)/ TAg) genetically engineered mouse mo del (GEMM) (Figure 1c). [score:3]
Similarly, although anti-miR-206 treatment elevated PDCD4, transfection of miR-206 mimic was suppressive (Figure 5a, middle and right panels). [score:3]
Consistent with studies that identified upregulation of miR-206 in ER [-] breast tumors, miR-206 levels were elevated in TNBCs compared with both ER [+] and HER2 [+] human subgroups (Figure 1a, right panel). [score:3]
These results are consistent with the direct regulation of miR-206 by KLF4 as previously reported. [score:3]
miR-206 is highly expressed in basal-like breast cancers and MaCSCs. [score:3]
3, 5 In TNBC cells, KLF4 directly regulates miR-206 transcription, and depletion of KLF4 consistently results in loss of the vast majority of miR-206. [score:3]
We next sought to determine whether miR-206 could have a causal role downstream of KLF4 to regulate MaCSC abundance. [score:2]
Furthermore, in TNBC cells we demonstrated the miR-206 regulation of a previously validated transcript, the gap junction protein connexin 43 (CX43/GJA1). [score:2]
We previously reported that RAS-ERK signaling, a prosurvival pathway, is maintained in TNBC cells by KLF4, in part through its regulation of miR-206. [score:2]
Our study, therefore, provides a rationale for miR-206-directed antago-miR therapy for the sensitization of the MaCSCs. [score:2]
62, 63, 64, 65, 66, 67, 68Consistent with its regulation by miR-206 in breast cancer cells, CX43 was increased in KLF4 -depleted MDA-MB-231 cells (Figure 6a, left panel). [score:2]
62, 63, 64, 65, 66, 67, 68 Consistent with its regulation by miR-206 in breast cancer cells, CX43 was increased in KLF4 -depleted MDA-MB-231 cells (Figure 6a, left panel). [score:2]
Similar regulation of P [+]/E [+] cell abundance by miR-206 was observed for SUM159PT cells (Figure 3d). [score:2]
57, 58, 59 We therefore analyzed PDCD4 as a miR-206-regulated transcript. [score:2]
DIANA-miRPath analysis identifies gap junction signaling as the top-ranked miR-206-regulated pathway (P=2.58 × 10 [−6]). [score:2]
These results establish miR-206 as a potential effector of KLF4 for regulation of MaCSC abundance. [score:2]
The critical role of endogenous miR-206 for tumor initiation following orthotopic injection, despite its minimal effects on cell proliferation or MaCSC abundance, pointed to a potential role in regulating cell survival. [score:2]
44, 45 Enrichment of miR-206 was similarly observed in murine basal-like mammary tumors (Figure 1b). [score:1]
Our studies identify KLF4 and miR-206 as functional MaCSC markers that mediate cell survival. [score:1]
Fragments of the PDCD4 3′ UTR containing two putative miR-206 -binding sites (denoted WT-A and WT-B; Figure 5b) were cloned downstream of the open reading frame of firefly luciferase (luc). [score:1]
32, 33, 35 Similar to KLF4, miR-206 was increased in human tumors of advanced histological grade (Figure 1a, left panel). [score:1]
These results suggest that endogenous KLF4 can signal through miR-206 to promote tumor initiation, probably by impacting cell survival rather than MaCSC abundance. [score:1]
Endogenous KLF4 and miR-206 promote tumor cell survival and in vivo tumorigenesis. [score:1]
miR-206 confers chemoresistance in TNBC cells. [score:1]
In support of a prosurvival role for endogenous miR-206, depletion of KLF4 sensitized TNBC cells to anoikis (Figure 4e). [score:1]
Consistent with miR-206 regulation of PDCD4 in MaCSCs, the P [+]/E [+] sub-population of MDA-MB-231 cells exhibited decreased levels of PDCD4 mRNA and protein compared with non-MaCSCs (Figure 5e). [score:1]
[38] Consistent with the elevated levels of miR-206 in MaCSCs, PDCD4 and CX43 levels were decreased. [score:1]
[10]We analyzed KLF4 and miR-206 levels in flow-sorted sub-populations of MDA-MB-231 cells (Figure 1d, left panel). [score:1]
[36] Despite the reduced levels of KLF4, miR-206 -transfected cells displayed higher P [+]/E [+] cell abundance relative to the control cells (Figure 3c, right panel). [score:1]
In TNBC cells, both KLF4 and miR-206 were critical for cell survival and in vivo tumor initiation. [score:1]
To study the role of endogenous miR-206 during in vivo tumorigenesis, we analyzed the tumorigenicity of MDA-MB-231 cells treated by in vitro transfection of anti-sense oligonucleotides (anti-miR-206). [score:1]
These results suggest that endogenous KLF4 exerts a prosurvival effect by induction of miR-206. [score:1]
71, 72, 73, 74 In skeletal muscle, miR-206 is important for repression of PAX7 during stem cell differentiation, and for muscle regeneration following injury. [score:1]
[10] We analyzed KLF4 and miR-206 levels in flow-sorted sub-populations of MDA-MB-231 cells (Figure 1d, left panel). [score:1]
In addition, we observed that either exogenous or endogenous miR-206 could promote malignant properties including tumor cell survival and drug resistance. [score:1]
These results identify KLF4 and miR-206 as MaCSC markers and potential mediators of MaCSC malignant properties. [score:1]
KLF4 and miR-206 are enriched in MaCSCs derived from human patient-derived xenografts (PDXs) and the C3(1)/ TAg GEMM KLF4 was similarly consistently elevated in lineage -negative (Lin [-])/ALDH [High] MaCSCs isolated from human mammary tumor tissues that were passaged as PDXs (Figure 2a). [score:1]
[37] In contrast to the prominent effect of miR-206 on tumor initiation and cell survival, on its own this miR has only limited effects on ERK activity. [score:1]
As expected, transfection of miR-206 mimic into MDA-MB-231 cells elevated the miR-206 level as detected by quantitative reverse transcription and PCR (qRT–PCR; Figure 3c, left upper panel). [score:1]
KLF4 and miR-206 are enriched in MaCSCs derived from human patient-derived xenografts (PDXs) and the C3(1)/ TAg GEMM. [score:1]
These results implicate miR-206 as an effector of KLF4 that promotes tumor initiation. [score:1]
Similarly, the P [+]/E [+] fraction of SUM159PT cells displayed elevated levels of KLF4 and miR-206, and showed a similar stem cell marker profile as the MDA-MB-231 cells (Figure 1e). [score:1]
Relative to the controls, in MDA-MB-231 cells miR-206 mimic repressed WT-reporter luc activity by 72%, and anti-miR-206 induced the reporter by 1.9-fold (Figure 5c). [score:1]
Effects on tumor growth were not likely attributed to differences in cell proliferation rates, as anti-miR-206 had little effect (Figure 4c, right panel). [score:1]
To determine the effect of KLF4-miR-206 signaling on MaCSC abundance, we depleted KLF4 in MDA-MB-231 cells using two distinct lentiviral short hairpin RNA constructs (Figure 3a, left upper panel). [score:1]
36, 37 In this study, we identified KLF4 and miR-206 as critical promoters of breast tumor cell survival. [score:1]
These results associate KLF4 and miR-206 with the MaCSC phenotype in human breast cancer mo dels. [score:1]
In contrast, exogenous KLF4 or miR-206 promoted MaCSC abundance, mirroring the role of exogenous KLF4 for generation of induced pluripotent stem cells. [score:1]
[36] In this study, we observed elevation of KLF4 and miR-206 in the P [+]/E [+] and ALDH [High] MaCSC fractions. [score:1]
Conversely, gain-of-function experiments showed that exogenous KLF4 promoted both miR-206 levels and the abundance of P [+]/E [+] cells (Figure 3b). [score:1]
7, 39, 40, 41, 42, 43 Indeed, consistent with our previous report that analyzed two human TNBC cell lines, [37] anti-miR-206 transfection sensitized several human TNBC mo dels and a murine basal-like mammary cancer mo del (that is, M6 cells) to anoikis (Figure 4d, left panel). [score:1]
Endogenous KLF4 and miR-206 promote tumor cell survival and in vivo tumorigenesisWe next examined the impact of endogenous KLF4-miR-206 signaling on tumor initiation. [score:1]
Collectively, these results link pluripotency factor signaling and the enhanced cell survival of MaCSCs, supporting roles of KLF4-miR-206 signaling for breast tumor cell survival, chemoresistance, and tumor initiation through the repression of PDCD4 and CX43 (Figure 7c). [score:1]
KLF4 and miR-206 can promote MaCSC abundance. [score:1]
50, 52 Similar to the human tumors, Lin [-]/ALDH [High] cells of C3(1)/ TAg mammary tumors also had increased Klf4 and miR-206 relative to ALDH [Low] cells (Figure 2c). [score:1]
[37] We therefore sought to better understand how endogenous miR-206 can promote anoikis resistance. [score:1]
18, 19 It will be interesting to determine whether miR-206 similarly influences the generation of induced pluripotent stem cells. [score:1]
7, 39, 40, 41, 42, 43 Finally, further documenting a prosurvival role, miR-206 promoted chemoresistance of TNBC cells against paclitaxel or doxorubicin. [score:1]
We next examined the impact of endogenous KLF4-miR-206 signaling on tumor initiation. [score:1]
In this study, we have identified endogenous KLF4 and a downstream effector, miR-206, as functional markers and prosurvival factors that are enriched in MaCSCs. [score:1]
[1 to 20 of 93 sentences]
6
[+] score: 231
Other miRNAs from this paper: hsa-mir-205, hsa-mir-548i-4
Figure 4(A) Venn diagram showing the overlap between genes down-regulated by ectopic expression of miR-206 and genes potentially targeted by miR-206 as predicted by Targetscan (Release 6.2) and miRDB (version 4.0). [score:10]
Further analysis of the microarray data indicated that miR-206 over -expression caused a significant preferential down-regulation of numerous predicted miR-206 targets (Supplementary Table 2). [score:8]
Figure 2(A– C) Over -expression of miR-206 inhibits growth, focus formation and anchorage-independent soft agar growth of Myc over -expressing cells. [score:7]
As expected, ectopic expression of miR-206 decreased endogenous MAP3K13 at the mRNA and protein levels in high Myc -expressing MB231 and HepG2 cancer cells but not in low Myc -expressing MCF-7 (Figure 4B–4C). [score:7]
In patients with Myc -high tumors, those with negative miR-206 expression and high expression of MAP3K13 had significantly worse survival than those with positive miR-206 and low MAP3K13 expression, respectively. [score:7]
Our data indicate that miR-206 inhibits Myc -driven human cancer by directly targeting MAP3K13. [score:6]
Using mRNA microarray technology, we generated a list of down-regulated genes (2-fold threshold) in miR-206–overexpressing HepG2 cells. [score:6]
This appears to be dependent on miR-206's ability to target MAP3K13 as indicated by our ability to recapitulate similar phenotypes by suppressing MAPK3K13 directly using an shRNA -based approach. [score:6]
Combining this list with the candidate list produced by 2 prediction algorithms, including miRDB (Version 4.0) and Targetscan (Release 6.2) [32– 33], we narrowed the miR-206 target candidates down to only 2 genes, including MAP3K13 and TPPP (Figure 4A). [score:5]
These findings are consistent with our bio-informatics -based analyses of gene expression profiles from the TCGA collection of breast cancers indicating that those tumors with the highest Myc levels tend, as a group, to express the lowest levels of miR-206 and the highest levels of MAP3K13 while simultaneously being associated with more adverse clinical outcomes. [score:5]
MiR-205 significantly decreased both anchorage -dependent and -independent growth in all three cell lines whereas miR-206 and miR-548i-4 inhibited growth only in the two cell lines with high level of Myc expression, namely MB231 and HepG2 (Figure 3A–3C and Supplementary Figure 2B–2D). [score:5]
Functional screening identifies miR-206 as a specific inhibitor of Myc-over -expressing cells. [score:5]
To further explore whether MAP3K13 represents a direct target of miR-206, we conducted luciferase reporter assays to determine whether the putative binding site of miR-206 in the 3′UTR of MAP3K13 is important for miR-206 mediated suppression. [score:5]
Figure 3(A–C) miR-206 inhibits growth, focus formation and anchorage-independent soft agar growth of Myc-over -expressing human cancer cells. [score:5]
By inhibiting MAP3K13, miR-206 inhibits the stability of Myc protein and thus of tumor cell survival and proliferation. [score:5]
Bottom: luciferase assays demonstrating that inclusion of the MAP3K13 3′UTR (wt) but not a mutant version of the sequence (mut) is down-regulated by miR-206 only in cell lines over -expressing Myc. [score:5]
In the presence of MycER activation, the ectopic expression of miR-206 significantly inhibited both anchorage -dependent and -independent growth (Figure 2A–2C) and promoted robust apoptosis (Figure 2D) relative to a control miR. [score:5]
Taken together, these data suggest that miR-206 selectively inhibits the growth of tumors expressing only the highest levels of Myc by reducing Myc transcript and protein, with the latter likely being due to protein de-stabilizination mediated by a loss of Ser62 phosphorylation. [score:5]
Future studies should focus on the phenotypes of MAP3K13 transgenic and knockout mice and whether miR-206 suppresses Myc -mediated tumorigenesis only in breast cancer or is a more general regulator. [score:5]
The expression of miR-206 is positively correlated with patient survival whereas the expression of MAP3K13 is inversely correlated. [score:5]
Thus, while miR-206 likely has multiple additional targets other than MAP3K13, it is this one in particular that appears to be the most important for generating a synthetic lethal effect in conjunction with Myc over -expression (Figure 2B and 2C). [score:5]
We extended this by demonstrating that miR-206 has a similar growth inhibitory effect on both the in vitro and in vivo proliferation of breast cancer cells, but only when they express high levels of Myc as would be expected of a classic synthetic lethal relationship (Figure 3) [21– 25]. [score:5]
The synthetic lethal relationship between Myc and the miR-206-MAP3K13 pathway likely reflects a different gene expression profile that exists in tumors with the highest levels of Myc expression. [score:5]
Overexpression of miR-206 is synthetically lethal with Myc overexpression. [score:5]
All these data strongly support the idea that miR-206 and MAP3K13 inhibits and promotes development of breast cancer by ultimately controlling Myc protein level, respectively. [score:4]
MAP3K13 is a direct target of miR-206. [score:4]
miR-206 directly targets MAP3K13. [score:4]
In summary, our study has demonstrated a significant role for miR-206 and MAP3K13 in regulating the viability of breast cancer cells with high levels of Myc expression. [score:4]
For miR-206, patients with any detectable signal or no signal were then assigned as having positive and negative gene expression, respectively. [score:3]
To study further the effects of miR-205, miR-206 and miR-548i-4 on Myc over -expressing cells, Hela-MycER and HepG2-MycER cells were stably transfected with expression vectors for each miR and the effects of MycER induction on cell growth, anchorage-independent growth and survival were measured. [score:3]
miR-206 was first reported to exert significant growth inhibition and to promote cell death in human breast, lung and liver cancers [41– 43]. [score:3]
miR-206 inhibits tumor growth of human cancer cells with high Myc levels. [score:3]
Hela-MycER and HepG2-MycER cells stably transfected with control or miR-206 expression vectors were used to construct growth curves to assess focus formation and anchorage-independentsoft agar growth. [score:3]
Supporting experiments revealed that forced expression of miR-206 produced higher levels of cleaved p25, indicating induction of apoptosis in both MB231 and HepG2 cells (Figure 3D). [score:3]
For miR-206, patients within the detected signal and non-detected signal were then assigned as having positive or negative gene expression, respectively. [score:3]
MCF-7, MB231 and HepG2 cancer cells stably expressing miR-206 or a control miR were used as described above for growth curves, focus formation, anchorage-independent soft agar growth and apoptosis detection. [score:3]
Although miR-206 did inhibit focus formation and anchorage independent soft agar growth somewhat in control HeLa-MycER and HepG2-MycER cells in the absence of 4-OHT, this effect was much greater in the presence of the compound (Figure 2B and 2C). [score:3]
Three miRs, miR-205, miR-206 and miR-548i-4 significantly inhibited all four cell lines by greater than two-fold under conditions of MycER activation (Figure 1C). [score:3]
Thus, of the three miRs identified in our initial HeLa-MycER screen, miR-205 and miR-206 demonstrated the most wide-ranging and robust synthetic lethal effect on Myc over -expressing cancer cells. [score:3]
Given that MAP3K13 appeared to be an important miR-206 target, we hypothesized that MAP3K13 would be important for Myc -driven human cancers. [score:3]
miR-206 impairs growth, clonogenicity and tumorigenicity of cancer cells expressing high levels of Myc. [score:3]
Indeed, ectopic miR-206 expression repressed the activity of a luciferase reporter containing a human MAP3K13 3′UTR whereas the same reporter containing a mutant miR-206 binding site was unaffected (Figure 4D). [score:3]
Thus, the human MAP3K13 mRNA is directly regulated by miR-206 via seed-matching sequences. [score:3]
Mechanistic studies revealed that enforced expression of miR-206 significantly decreased Myc transcripts, total Myc protein and its transcription activity (Figure 3F–3H). [score:3]
Identifying miR-206 targets is critical for understanding its biological functions. [score:3]
To investigate the potential roles of miR-205, miR-206 and miR-548i-4 on the growth of cell lines with different levels of endogenous Myc expression, we next stably expressed each of the three miRs in MCF-7 and MB231 breast cancer and HepG2 hepatocarcinoma cells (Supplementary Figure 2A). [score:3]
These results strongly supported the idea that MAP3K13 is essential for tumor growth of human cancer cells with high Myc levels and that it is the major, if not the sole, functional target of miR-206. [score:3]
If so, these data would predict that Myc -high human breast cancers with correspondingly high MAP3K13 or low miR-206 expression may correlate with poor survival. [score:3]
Primers for the constructs and mutations are listed in Supplementary Table 3. For luciferase assays, MCF7, MB-231, HepG2 and HEK293 cells were seeded in 24-well format dishes and transfected with the indicated firefly luciferase reporter plasmid, Renilla reporter plasmid, in a PGL3-vector with HSV TK Promoter, as a normalization control and miR-206 or a negative control expression vector. [score:2]
Mutations in the miR-206 seed-matching sequences were generated by overlap extension PCR. [score:2]
miR-206 directly decreases MAP3K13 mRNA and protein levels. [score:2]
Further investigation has revealed that the link between miR-206 and Myc involves the suppression of MAP3K13, a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that has previously been reported to activate both the NF-κB and JUN pathways [30]. [score:1]
miR-206 is indicated in red. [score:1]
We found that the 3′-UTR of MAP3K13 contains one miR-206 binding site across all database analyses (Figure 4D). [score:1]
miR-206 was identified as one such miR that exerted a potent anti-proliferative effect in a mo del in vitro system. [score:1]
We then determined whether levels of miR-206 or MAP3K13 correlated with patient survival in the Myc -high or Myc-low groups. [score:1]
But at least we found that miR-206's effect on Myc was also mediated through MAP3K13. [score:1]
Human Pri-miR-206, including approximately 400 bp of stem-loop structures, was polymerase chain reaction (PCR)-amplified from genomic DNA and cloned into the lentiviral vector pHAGE-CMV-MCS-PGK-GFP. [score:1]
miR-206 also decreases Myc mRNA level (Figure 3F) and it is possible miR-206 through other pathway to affect Myc in mRNA level. [score:1]
The GenBank accession numbers used for c-Myc, MAP3K13 and miR-206 were NM_001706, NM_004721 and NR_029713, respectively. [score:1]
These data indicate that Myc activation leads to a decreased and increased dependency on miR-206 and MAP3K13 in human breast cancers, respectively. [score:1]
Myc, MAP3K13 and miR-206 expression data were assessed and Kaplan Meier curves were calculated in human breast cancer tissues from the TCGA mRNA or miR-seq data set (n = 1044). [score:1]
Nucleotides mutated in the miR-206 -binding site are shown in red. [score:1]
[1 to 20 of 63 sentences]
7
[+] score: 208
Other miRNAs from this paper: hsa-mir-34a
These elucidates that the phenotypic effects of migration and invasion observed after HOTAIR inhibition, at least in part, through the regulation of MKL1 via inhibition of miR206 expression in HeLa cells. [score:8]
In conclusion, we have performed that HOTAIR exerts its effects on migration and invasion of cancer cells, at least in part, through the regulation of MKL1 expression via inhibition of miR206 expression. [score:8]
The second mechanism is that HOTAIR regulated MKL1 expression via inhibition of miR206 expression. [score:8]
Furthermore, MKL1 was down-regulated by miR206 via targeting its 3-UTR, as a potential target gene of miR206 in HeLa cells. [score:8]
Moreover, the expression level of MKL1, as the targeting gene of miR206, was decreased after HOTAIR inhibition in HeLa cells. [score:7]
Contrasted with miR-206 inhibitor, co -transfected miR-206 inhibitor and siMKL1 reversed the effect of miR-206 inhibition on cell invasion. [score:7]
However, the miR-206 inhibitor decreased the miR-206 RNA expression level (Fig. 5c ) and increased MKL1 expression (Fig. 5d ). [score:7]
In this study, we have demonstrated that the protein expression of MKL1 was increased after inhibition HOTAIR, and miR-206 also mediated the expression of MKL1. [score:7]
Together, these data suggest that HOTAIR exerts its effects on migration and invasion of cancer cells, at least in part, through the regulation of MKL1 via inhibition of miR206 expression in HeLa cells. [score:6]
Mutation contains 4-base-mutation at the miR-206 targeting region, abolishing its binding. [score:5]
c qRT-PCR was used to measure the efficiency of miR-206 inhibition after transfecting miR-206 inhibitor at 48 h. The expression level of miR-206 was normalized to U6. [score:5]
Contrasted with miR-206 inhibition, the cells migration was significant reduced after co-transfecting miR-206 inhibition and siMKL1 (Fig. 6c & d). [score:5]
All the data suggested that miR-206, as a potential targeting miRNA against MKL1, degraded MKL1 by targeting the specific sites in HeLa cells. [score:5]
d Western blots analysis of the MKL1 protein expression at 48 h after transfected with miR-206 inhibitor or NC. [score:5]
In order to further study that whether miR-206 expression was associated with migration and invasion of cancer cells, we transfected miR-206 mimics or inhibitor in HeLa cells using transfection reagent RNAi-mate. [score:5]
And, the expression of miR206 were significantly down-regulated in cervical cancer, compared with adjacent normal tissues [76]. [score:5]
To further demonstrate the direct regulation of MKL1 by miR-206, we constructed luciferase reporters with the targets sequences of wile-type (WT-UTR) and mutated MKL1 3`-UTRs (mut-UTR). [score:5]
MiR206, as a tumor suppressor, regulated several oncogenes expression in various types of tumor cancers. [score:5]
As shown in Fig. 7b, the abundance of HOTAIR in HeLa cells reduced more than 60% at 48 h. And the RNA expression level of miR-206 exhibited a dramatic decrease at 48 h after HOTAIR inhibition (Fig. 7c ). [score:5]
In this study, we further confirmed that knockdown HOTAIR could enhance miR206 RNA expression level in HeLa cells. [score:4]
Meanwhile, the number of invaded cells decreased significantly after co-transfecting miR-206 inhibitor and siMKL1, compared with miR-206 inhibition cells (Fig. 6g & h). [score:4]
HOTAIR regulated expression of miR-206. [score:4]
c The effect of inhibition miR-206 using miRNA inhibiton on cell migration was determined by wound healing assay. [score:4]
b Western blots analysis of the MKL1 protein expression at 48 h after transfected with miR-206 mimics or NC. [score:3]
a HeLa cells were transfected with miR-206 mimics or NC for 48 h. The abundance of miR-206 expression was determined by qRT-PCR. [score:3]
HeLa cells were transfected with siHOTAIR or siNC for 48 h. c. The RNA expression of miR-206 after transfecting siHOTAIR at 48 h by qRT-PCR. [score:3]
The expression level of miR-206 was normalized to U6. [score:3]
Our results showed that increased miR206 expression could significantly slow down the migration and invasion in HeLa cells. [score:3]
miR-206 could target 3’-UTR of MKL1 by two algorithms predicted. [score:3]
What is more, co-transfection of HeLa cells with miR-206 inhibition and siMKL1 abrogated effects of miR-206 mimics on cell migration (Fig. 6c & d). [score:3]
After transfected miR-206 mimics at 48 h, the RNA expression level of miR-206 was significantly increased (Fig.   5a ), and the protein MKL1 was obviously decreased (Fig. 5b ). [score:3]
Based on these results, we proposed that miR-206 inhibited cell migration and invasion in HeLa cells, and MKL1 could partially abrogate these effects of miR-206. [score:3]
MKL1 is a downstream target of miR-206. [score:3]
In contrast, inhibition miR-206 increased the capability of invasiveness in HeLa cells in comparing with negative control (Fig. 6g & h). [score:3]
In contrast, miR-206 inhibition increased the cell migration significant (Fig. 6c & d). [score:3]
HOTAIR MKL1 miR206 Migration Invasion At least, 90% of the human genome is actively transcribed into non-coding RNAs (ncRNAs) [1], which are implicated in the regulation of multiple major biological processes impacting development, differentiation, and metabolism [2]. [score:3]
In order to further identify that miR-206 targeted 3`-UTR of MKL1 by the predicted sites, we mutated 4 bases in the predicted sites (Fig. 5e ). [score:3]
As shown in Fig. 6e & f, the number of invaded cells decreased significantly in miR-206 overexpression cells by transfecting miR-206 mimics in comparison with the negative control. [score:3]
To the contrary, the effects were enhanced after transfecting miR206 inhibition. [score:3]
As shown in Fig. 7a, the majority of the HOTAIR or miR-206 expression were detected in cytoplasm in HeLa cells using the junction probes. [score:3]
Importantly, HOTAIR is observed to participate in the silencing of miR206 expression. [score:3]
Site-directly mutant was used to change the binding sites of miR-206 in the 3’UTR of MKL1. [score:2]
a The effect of expression miR-206 using miRNA mimics on cell migration was determined by wound healing assay. [score:2]
*, P < 0.05; **, P < 0.01 (Student’s t test) MiR206, as a tumor suppressor, plays important roles in tumorigenesis and tumor progression of various human malignancies [55– 57]. [score:2]
Quantitative analysis of miR-206 expression was assayed using a Hairpin-it miRNA real-time PCR Quantitation Kit (GenePharma, Shanghai, China). [score:2]
This data indicated HOTAIR could be a potential negative regulator of miR-206 in HeLa cells. [score:2]
a Detect the localization of HOTAIR and miR-206 by RNA FISH in HeLa cells. [score:1]
Fig. 7Detect the localization of HOTAIR and miR-206 by RNA FISH in HeLa cells. [score:1]
Effect of miR-206 on cells migration and invasion in HeLa cells. [score:1]
Comparing with negative control, miR-206 mimics resulted in a significant decrease of cell migration in HeLa cells (Fig.   6a & b). [score:1]
Whether there was a relationship between HOTAIR and miR206 remained to be explored. [score:1]
To investigate the relation between HOTAIR and miR-206, we firstly detected the distribution of HOTAIR and miR206 using RNA-fluorescence in situ hybridization (RNA-FISH) technology, ensuring the expression abundance. [score:1]
The seed sequence of miR-206 was underlined. [score:1]
RNA-FISH, as an indispensable tool for the detection and localization of RNA, was used to study the distribution of HOTAIR and miR-206. [score:1]
Fig. 6Effect of miR-206 on cells migration and invasion in HeLa cells. [score:1]
And the probe of miR-206 was purchased from Invitrogen. [score:1]
And the probe of miR-206 was labelled with FAM. [score:1]
MiR-34a and miR-206 act as novel prognostic and therapy biomarkers in cervical cancer. [score:1]
[1 to 20 of 58 sentences]
8
[+] score: 204
Other miRNAs from this paper: hsa-mir-221, hsa-mir-222, hsa-mir-1-2, hsa-mir-1-1
In addition, miR-206 overexpression downregulated Notch3 and Bcl-2 expression and upregulated Bax and caspase-3 expresssion at the protein level, as shown by western blot analysis (Fig. 6); the protein expression of cleaved caspase-3 (caspase-3 CL) in particular was markedly increased. [score:15]
Our results revealed that the overexpression of miR-206 markedly downregulated Hes1 expression, significantly elevated p57 expression, and finally induced cell cycle G1 phase blockage in the HepG2 cells. [score:10]
However, our results revealed that Notch3 was downregulated with the overexpression of miR-206; Bax expression was increased at the mRNA and protein levels, Bcl-2 expression was significantly reduced, and, finally, caspase-3, which exhibited a similar effect to GSI (25), was activated. [score:10]
Consistent with the results of migration assay, the overexpression of miR-206 caused a significant reduction in MMP-9 expression at the mRNA and protein level (Figs. 3B and 6); the protein expression level of cleaved MMP-9 (MMP-9 CL) in particular was downregulated in the HepG2 cells. [score:9]
In the present study, we demonstrated that miR-206 inhibited cell migration through the Notch3-MMP-9 pathway, partly due to its effect on MMP-9. Although we suggested Notch3 is likely to be a direct target gene of miR-206 in HepG2 cells, further studies are required to identify any other mRNAs that are directly regulated by miR-206 in HepG2 cells, as previously reported in other cell lines (12, 13, 30– 32). [score:8]
It has been demonstrated that several target mRNAs are directly regulated by miR-206, including Cdc42, estrogen receptor α (ERα), Notch3, liver X receptor α (LXRα), high mobility group box 3-like pseudogene (Hmgb3) and c-Met (12– 13, 15, 30– 32), among which Notch3 was hypothesized to be a direct target gene of miR-206 in this study. [score:8]
Recent studies (41, 42) have shown that miR-206 expression is significantly downregulated in gastric and breast cancer tissues when compared with their normal adjacent tissues, which significantly correlates with tumor progression, suggesting that miR-206 acts as a tumor suppressor. [score:7]
Our results indicate that one of the possible mechanims responsible for the inhibitory effects of miR-206 on the migration of HepG2 cells is through the Notch3-MMP-9 pathway, at least through the downregulation of MMP-9. Immunostaining revealed a high Notch3 protein expression in the cytoplasm of the neoplastic hepatocytes in 12 out of the 12 (100%) HCC samples compared with occasional weak hepatocytic staining in their corresponding adjacent non-neoplastic tissue samples. [score:7]
However, it is a worth noting that Song et al first identified an almost perfect complementarity between miR-206 and the 3′-untranslated regions (3′-UTRs) of both mouse and human Notch3 and found that the ectopic expression of miR-206 induced apoptotic cell death in HeLa cells, which was associated with its inhibition of Notch3 signaling (15). [score:7]
Our results indicate that one of the possible mechanims responsible for the inhibitory effects of miR-206 on the migration of HepG2 cells is through the Notch3-MMP-9 pathway, at least through the downregulation of MMP-9. An abundance of in vivo and in vitro studies has indicated that enhanced cell proliferation, resistance to apoptosis and the migration state of HCC cells plays an important role in the progression of HCC (2, 8). [score:6]
The relative protein level was used to evaluate the differences in protein expression between the miR-206 -treated group and the NC group; the relative protein level = (IOD ratio between the target gene product bands and the β-actin protein bands in the miR-206 -treated group)/(IOD ratio between the target gene product bands and the β-actin protein bands in the NC group). [score:5]
Despite increasing evidence pointing to a role for miR-206 as a tumor suppressor, the tumor suppressive effect of miR-206 has not been fully elucidated. [score:5]
Similarly, Chen et al found that miR-206 overexpression suppressed ERα and induced the cell cycle arrest of ERα -positive epithelial endometrial cells (EECs) (13). [score:5]
Of note, we found that the enforced overexpression of miR-206 markedly attenuated Notch3 expression at the mRNA and protein level in the HepG2 cells, these results are consistent with those of other studies on other cell lines (1, 15). [score:5]
We found that miR-206 significantly suppressed tumor growth and metastasis at least in part by targeting the Notch3 signaling pathway in vitro. [score:5]
The ectopic expression of miR-206 has been shown to inhibit the growth of rhabdomyosarcoma (RMS) (10), breast cancer (11, 12), endometrial endometrioid carcinoma (EEC) (13), lung cancer (14) and HeLa cells (15). [score:5]
Taken together, our results demonstrate that miRNA-206 overexpression promotes apoptosis, induces cell cycle arrest and inhibits the migration of HCC HepG2 cells. [score:5]
It was hypothesized that Notch3 is a direct target gene of miR-206 in HCC cells. [score:4]
Of note, these data support our hypothesis that Notch3 is likely to be a direct target gene of miR-206 in HepG2 cells. [score:4]
Therefore, to a certain extent, this result supports our hypothesis that Notch3 is a direct target gene of miR-206 in HepG2 cells. [score:4]
In the present study, both the mRNA and protein levels of MMP-9 were downregulated in the miR-206 -transfected cells, which significantly impaired the migratory capability of HepG2 cells. [score:4]
Moreover, qRT-PCR analysis revealed that the relative expression of Notch3 and Bcl-2 was markedly reduced, whereas that of Bax was increased at the mRNA level following transfection with miR-206 (Fig. 3B). [score:3]
Flow cytometric analysis indicated that miR-206 overexpression slowed down cell cycle progression and caused cell cycle G1 phase blockage in the HepG2 cells (Fig. 7A). [score:3]
We also found that elevated miR-206 levels inhibited the growth of HepG2 cells, which was associated with the induction of apoptosis and cell cycle arrest. [score:3]
There was an approximately 2.0- or 3.0-fold increase in the percentage of apoptotic cells in the HepG2 cells overexpressing miR-206 (Fig. 5B and D). [score:3]
Inhibition of cell proliferation following transfection with miR-206. [score:3]
Moreover, miR-206 inhibited the growth of HepG2 cells by inducing cell cycle arrest. [score:3]
miR-206 overexpression promotes apoptotic cell death in HepG2 cells. [score:3]
To the best of our knowledge, this study is the first to reveal the function and possible underlying mechanisms of action of miR-206 in HCC and suggests that miR-206 has the potential for use in the targeted therapy of HCC. [score:3]
These results indicate that miR-206 overexpression decreases the proliferation of human hepatocellular carcinoma HepG2 cells. [score:3]
Thus, the issue of whether miR-206 induces cell cycle arrest in HCC cell lines by inhibiting ERα, remains to be addressed further. [score:3]
We found that the miR-206 mimic -treated cells had an approximately 60-fold greater expression of mature miR-206 than the cells transfected with the negative control mimic (Fig. 3A). [score:3]
Therefore, further studies are required to elucidate all the aspects of miR-206 expression in HCC. [score:3]
In order to discover the probable underlying mechanisms of action of miR-206 in inducing cell cycle arrest, we further analyzed the expression of Hes1 and p57 in HepG2 cells at the mRNA and protein level. [score:3]
miR-206, a member of the muscle-specific miR-1 family of muscle-specific microRNAs (myomiRs), is a skeletal muscle-specific miRNA involved in muscle development (9). [score:2]
To the best of our knowledge, the present study is the first to explore the function and probable underlying mechanisms of action of miR-206 in HCC HepG2 cells. [score:1]
Cy3 -modified miR-206 mimic and Cy3 -modified mimic negative control were purchased from RiboBio Co. [score:1]
Cellular migration is impaired following transfection with miR-206 in HepG2 cells. [score:1]
Cell proliferation was significantly decreased in the cells following 48 h of transfection with miR-206 (Fig. 4). [score:1]
Furthermore, the mRNA levels of miR-206 were analyzed by qRT-PCR. [score:1]
Thus, our results indicate that the pro-apoptotic effect of miR-206 in HepG2 cells is at least partially dependent on Notch3 -mediated mitochondrial apoptotic signaling. [score:1]
There seems to be a doubt as to whether there is a similar interaction between miR-206 and Notch3. [score:1]
Representative immunostaining patterns of the Notch3 expression are shown in Fig. 1. To investigate the functional role of miR-206, Cy3 -modified miR-206 mimic and Cy3 -modified mimic negative control were successfully transiently transfected into the HepG2 cells (Fig. 2). [score:1]
Cell invasive and migratory ability has also been shown to be impaired by miR-206 in RMS (10), EEC (13), lung cancer (14) and HeLa cells (15). [score:1]
For convenience, Cy3 -modified miR-206 mimic and Cy3 -modified mimic negative control were simply referred to as miR-206 and negative control (NC), respectively. [score:1]
However, studies have revealed that miR-206 is closely related to various tumors. [score:1]
miR-206 induces cell cycle arrest in HepG2 cells. [score:1]
Although the multiple anticancer functions of miR-206 have been confirmed, its underlying anticancer mechanisms of action are not yet fully understood. [score:1]
Taken together, our results indicate that the effects of miR-206 on the cell cycle (causing cell cycle arrest) are possibly mediated through the crosstalk between these 3 genes (Notch3-Hes1-p57 signaling) in the HepG2 cells. [score:1]
Secondly, miR-206 mimic and mimic negative control were successfully transfected into the HepG2 cells. [score:1]
However, to the best of our knowledge, our study is the first to reveal the function and possible underlying mechanisms of action of miR-206 in HCC HepG2 cells. [score:1]
Thus, we examined the cellular migration ability in order to explore the potential role of miR-206 in HCC cell metastasis. [score:1]
Furthermore, these results indicate that the pro-apoptotic effect of miR-206 in HepG2 cells is at least partially dependent on Notch3 -mediated mitochondrial apoptotic signaling. [score:1]
MMPs may be associated with the impaired migtation of miR-206 -transfected cells. [score:1]
Furthermore, fluorescence-activated cell sorting (FACS) has demonstrated that miR-206 activates apoptosis in lung cancer (14) and HeLa cells (15) and induces cell cycle arrest at the G0/G1 phase of the cell cycle in RMS (10) and EEC cells (13). [score:1]
In addition, cellular migration was also impaired following transfection with miR-206 in the HepG2 cells. [score:1]
The miR-206 -treated group showed increased numbers of Hoechst 33342 positively stained cells 48 h after transfection, indicating an enhanced apoptotic activity (Fig. 5A–b). [score:1]
For the qRT-PCR detection of mature miR-206 expression, we purchased the Bulge-Loop™ miRNA qRT-PCR Primer Set and the miRNA qRT-PCR Control Primer Set (both from RiboBio). [score:1]
miR-206 mimics were transiently transfected into HepG2 cells. [score:1]
The cells were washed with PBS and then transiently transfected with 100 nM miR-206 or NC using Lipofectamine™ 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. [score:1]
[1 to 20 of 60 sentences]
9
[+] score: 183
Knockdown or ectopic upregulation of miR-206 alters KLF4 levels in human colon cancer cellsIn an initial screen of human colon cancer cell lines (Figure 4), SW48 cells had the highest constitutive levels of miR-206 and low relative expression of KLF4, whereas SW480 cells exhibited the highest endogenous KLF4 levels and low miR-206 expression. [score:9]
In a panel of primary human colon cancers, target validation at the mRNA and protein level confirmed a significant inverse relationship between miR-206 and KLF4, which was further supported by miR-206 knockdown and ectopic upregulation in human colon cancer cells. [score:7]
In cells with intermediate constitutive levels, forced expression or knockdown of miR-206 resulted in the expected reciprocal changes in KLF4, and miR-206 ectopic upregulation increased cell proliferation kinetics in real-time monitoring assays. [score:6]
However, low-abundance miRNAs, such as miR-206, are often among the most significantly upregulated miRNAs relative to their expression in normal non-transformed tissues. [score:6]
Figure 5 Knockdown and ectopic upregulation of miR-206 reciprocally regulates KLF4. [score:6]
In contrast, HCT116 cells treated with miR-206 inhibitor had a significant reduction in miR-206 expression, and this was associated with a corresponding increase in KLF4 (compare pink bars in Figure 5A and 5B). [score:5]
Carcinogen -induced colon tumors and adjacent normal-looking colonic mucosa from a prior study [22] were examined for (A) miR-206 expression, normalized to RNU6B, and (B) Klf4 mRNA expression normalized to Gapdh. [score:5]
Recently, a KLF4/miR-206 autoregulatory feedback loop was reported to regulate protein translation reciprocally in normal and cancer cells [12]. [score:5]
An inverse correlation was noted between miR-206 and KLF4 in a panel of human primary colon cancers, which was supported by experimental studies involving knockdown and ectopic upregulation of miR-206 levels in human colon cancer cells. [score:5]
Increased miR-206 and attenuated Klf4 expression in rat colon tumorsAmong 679 unique miRNAs profiled, miR-206 was the most dramatically altered miRNA in rat colon tumors, exhibiting ~73-fold higher expression relative to the corresponding normal-looking colonic mucosa (microarray data not shown). [score:5]
In an initial screen of human colon cancer cell lines (Figure 4), SW48 cells had the highest constitutive levels of miR-206 and low relative expression of KLF4, whereas SW480 cells exhibited the highest endogenous KLF4 levels and low miR-206 expression. [score:5]
Knockdown or ectopic upregulation of miR-206 alters KLF4 levels in human colon cancer cells. [score:5]
Studies in breast cancer mo dels have reported tumor suppressive effects of miR-206 due to its pro-apoptotic properties, via the inhibition of notch3 signaling and cell migration [9, 33] or proliferation [10]. [score:5]
In a separate study using azoxymethane as the initiating agent, miR-206 was also significantly upregulated (~100-fold) in rat colon tumors [34]. [score:4]
Interestingly, however, when the dataset of 679 miRNAs was taken in its entirety, the low-abundance miR-206 was identified as the most significantly upregulated (up to 73-fold) in rat colon tumors relative to normal colonic mucosa. [score:4]
Furthermore, miR-206 was one of five miRNAs that exhibited stage -dependent differential expression in human colorectal cancers [33]. [score:3]
Human HCT116 colon cancer cells were transfected with increasing concentrations of a miR-206 mimic (graded orange-shaded bars indicating increasing miR-206), or miR-206 inhibitor (pink bars). [score:3]
There was an inverse association between miR-206 levels and KLF4 mRNA expression among the 21 human primary colon cancers examined (Figure 3A, inset, r [2] = 0.525, P < 0.05). [score:3]
Data bars indicate mean ± SD, n = 3. Among 679 unique miRNAs profiled, miR-206 was the most dramatically altered miRNA in rat colon tumors, exhibiting ~73-fold higher expression relative to the corresponding normal-looking colonic mucosa (microarray data not shown). [score:3]
Among the other factors that might contribute in vitro, miR-206 expression was influenced by cell confluency, being about threefold higher at 70% versus 20% confluency (MAP et al., unpublished data). [score:3]
Putative target mRNAs of miR-206 were examined via MetaCore pathway analysis (GeneGo Inc. [score:3]
Forced expression of miR-206 resulted in significantly increased cell proliferation kinetics, as revealed by real-time monitoring using HCT116 cells. [score:3]
A dose -dependent increase in miR-206 expression was observed on transfecting cells with miR-206 mimic (30 to 70 nM), relative to untreated cells (black bar), vehicle treatment (30 and 40 μl HiPerFectamine, blue bars), or sham control (green bars). [score:3]
For human primary colon cancers and their matched controls, miR-206 and KLF4 expression values were analyzed by Benjamini-Hochberg correction using ArrayStar software (DNASTAR, Inc. [score:3]
Final concentrations were as follows: miR-206 mimic 30–70 nM, miR-206 inhibitor 50 and 75 nM, AllStars Negative Control 25–75 nM, or HiPerFectamine 30–40 μl in 1000 μl serum-free McCoy’s 5A medium. [score:3]
This subset of cancers would differ from the more typical scenario involving increased miR-206 and reduced let-7a expression. [score:3]
In contrast to these observations, cancers of the breast and lung have been characterized as exhibiting low miR-206 expression levels, suggesting a possible tumor suppressor function [9, 10, 12]. [score:3]
Moreover, levels of miR-206 were inversely proportional to c-met expression, an important proto-oncogene in rhabdomyosarcoma [11]. [score:3]
Given that let-7 family members are normally ascribed a tumor suppressor function, the authors speculated that a high let-7a/low miR-206 ‘signature’ might designate colon tumors with a unique phenotype in terms of cancer progression, compartmentalization, or microenvironment [33]. [score:3]
Metacore pathway analysis predicted multiple targets of miR-206, including KLF4 (Figure 1A), which was further supported by sequence complementarity alignment (Figure 1B). [score:3]
Figure 2 miR-206 and Klf4 expression in rat colon tumors. [score:3]
Computational mo deling highlighted the stem-cell marker Krüppel-like factor 4 (KLF4) as a potential target of miR-206. [score:3]
Increased miR-206 and attenuated Klf4 expression in rat colon tumors. [score:3]
Further studies are in progress on the role of pluripotency factors, cancer stem markers, and other potential molecular targets of the miR-206/ KLF4 axis (Figure 1). [score:3]
Interestingly, Caco-2 cells resembled non-transformed CCD841 cells, as well as certain human primary colon cancers (Cases 9 and 15, Figure 3), in having low expression levels of both miR-206 and KLF4. [score:3]
Figure 4 Constitutive expression of miR-206 and KLF4 in human colon cancer cells. [score:3]
Located on chromosome 6p12.2, miR-206 is similar in expression and function to miR-1, but its sequence differs by four nucleotides [32]. [score:3]
This investigation has focused on the possible role of miR-206 and one of its predicted targets, KLF4, in colon cancer development. [score:2]
These data supported a possible role for miR-206 regulating Klf4 in some but not all rat colon tumors. [score:2]
This investigation, therefore, sought to clarify the role of miR-206 and its putative target KLF4 in colon cancer development. [score:2]
Lin et al. [12] identified an autoregulatory feedback loop between miR-206 and Krüppel-like factor 4 (KLF4). [score:2]
As noted in the rat mo del, the inverse association between miR-206 and KLF4 was not always apparent; for example, Case 9 exhibited low relative expression of both miR-206 and KLF4 in the cancer compared with the patient-matched control (Figure 3B,C). [score:2]
However, we did note that one colon tumor with a high relative level of miR-206 did not exhibit a correspondingly reduced level of Klf4 (compare data in Figures 2A and 2B for Case 3). [score:1]
Figure 3 Inverse association between miR-206 and KLF4 in human colon cancers. [score:1]
Figure 6 Cell proliferation is increased by miR-206. [score:1]
HCT116 human colon cancer cells were transfected with miR-206 mimic, as described previously. [score:1]
As predicted by computational mo deling, a significant inverse relationship was noted between miR-206 and KLF4 (Figure 3A, inset). [score:1]
To provide further proof-of-concept, we examined a panel of human colon cancer cell lines and noted that SW480 and SW48 cells provided the best evidence for an inverse association between miR-206 and KLF4. [score:1]
An inverse relationship between miR-206 and KLF4 in human primary colon cancers. [score:1]
For the six colon tumors shown, data bars indicate mean ± SD, n = 3. An inverse relationship between miR-206 and KLF4 in human primary colon cancersBased on a prior report [25], human primary colon cancers were first screened for a suitable endogenous control (data not shown); miR-191 was selected for subsequent qRT-PCR analyses. [score:1]
Thus, we next examined a panel of human primary colon cancers and detected increased miR-206 levels in ~50% of the cases. [score:1]
Under the same conditions, enforced increase of miR-206 resulted in loss of KLF4 (compare orange bars in Figure 5B with those in Figure 5A). [score:1]
Unbiased screening of over 650 miRNAs identified miR-206, a low-abundance miRNA, as the most significantly altered miRNA in carcinogen -induced rat colon tumors. [score:1]
Interestingly, the latter report noted, in contrast to the current study, that miR-206 levels were more typically attenuated whereas let-7a was increased in the cancers. [score:1]
Figure 1 The miR-206/KLF4 axis in colon cancer. [score:1]
One such candidate is miR-206. [score:1]
Specifically, for miR-206 the tumor mean ± SD was 1.8 × 10 [−5] ± 4.5 × 10 [−7] versus matched controls 2.8 × 10 [−6] ± 4.6 × 10 [−6] (P < 0.0001, n = 6). [score:1]
Transfection of HCT116 cells was performed using a miR-206 mimic (Qiagen, Valencia, CA, USA). [score:1]
As a low-abundance miRNA, miR-206 might have been overlooked but for the fact that it was the most significantly increased miRNA in rat colon tumors, relative to normal colonic mucosa. [score:1]
MicroRNA arrays [22] identified miR-206 as a low-abundance miRNA with potentially important roles in carcinogen -induced rat colon tumors. [score:1]
Caco-2 cells exhibited low endogenous levels of both miR-206 and KLF4, similar to the non-cancer colon embryonic epithelial cell line CCD841 (Figure 4, solid black bar). [score:1]
For miR-206, the tumor mean ± SD was 1.8 × 10 [−4] ± 1.6 × 10 [−5] versus 1.3 × 10 [−4] ± 4.6 × 10 [−6] in matched controls (P < 0.05). [score:1]
Nonetheless, we were intrigued that two quite different colon carcinogens increased miR-206 so dramatically in colon tumors, relative to normal colonic mucosa. [score:1]
This report provides the first comprehensive analysis of the miR-206/KLF4 axis in parallel studies involving a preclinical colon carcinogenesis mo del, human primary colon cancers, and a panel of human colon cancer cells. [score:1]
These findings supported an inverse association between miR-206 and KLF4 in colon cancer. [score:1]
Enforced increase of miR-206 levels augments proliferation kinetics in human colon cancer cells. [score:1]
The latter report did not pursue miR-206 further, owing to its low abundance relative to other miRNAs. [score:1]
[1 to 20 of 67 sentences]
10
[+] score: 173
Comparison of female patients with female controls resulted in significant 5.4 fold upregulation of miR-206 (p = 0.02), 2-fold upregulation of miR-133b (p = 0.03) and 1.4 fold upregulation of miR-145 (p = 0.04) (Figure S5B). [score:10]
Although miR-206 is the only myomir whose expression was described to be striated muscle-specific, it has subsequently been shown to be expressed also in brown fat [59], in liver [60], in subset of helper T-cells [61], and in breast tissue where its expression may be under hormonal control [62]. [score:7]
miR-206 expression is controlled by myogenic regulatory transcription factors including myogenin and MyoD that are also upregulated by denervation [49]– [51]. [score:7]
At symptomatic P90, miR-206 was 7.7 fold upregulated in EDL (p = 0.0001), 4.5 fold upregulated in plasma (p = 0.0004). [score:7]
Here, however, miR-206 upregulation in SOD1-G93A mice was not associated with miR-133b upregulation at any stage. [score:7]
Both genders combined, the qPCR analysis (Figure 4) indicated 4.3 fold upregulation of miR-206 (p = 0.005) and 2 fold upregulation of miR-106b (p = 0.02) in patient versus control serum samples. [score:7]
miR-206 is important for differentiation of myoblasts as it downregulates of several inhibitors myogenesis [67]. [score:6]
Upregulation of miR-206 in male EDL and plasma was close to significance at presymptomatic stage, which suggests that the threshold of fast muscle denervation at which miR-206 expression is induced is crossed between postnatal days 60 and 90, where also the myogenic factors involved in miR-206 transcription are induced [23]. [score:6]
Therefore, although severe muscle atrophy could dampen miR-206 expression directly, this is not supported at least in males where the most severely damaged EDL shows the highest miR-206 expression. [score:6]
The increase in the levels of miR-206 was first significant in the symptomatic stage, consistent with its upregulation in denervated tibialis anterior (TA) muscle and in symptomatic TA muscle of a similar ALS mo del [44]. [score:4]
At terminal P120, miR-206 was 11.7-fold upregulated in male EDL muscle (p = 0.0001) but, perhaps surprisingly, showed a −40% decrease in circulating plasma (p = 0.04). [score:4]
Comparison of male patients with male controls did not result in significant changes, although miR-206 was close to significance (3.4 fold upregulation, p = 0.1, Figure S5A). [score:4]
Instead, miR-206 upregulation is required for formation of new NMJs after nerve injury and contributes to the capability to maintain neuromuscular connections in SOD1-G93A animals in vivo by potentiating the function of muscle-derived factors on NMJ regeneration [44]. [score:4]
Whether miR-206 and miR-106b have a functional role in human ALS pathogenesis needs further experimental focus, preferably using methodology that can reveal miRNA target genes and pathways directly in the affected tissues. [score:4]
At P90, miR-206 was 7.1 fold increased in EDL (p = 0.0001, Figure 3A) and its upregulation was suggestive but non-significant in P90 plasma (3.3 fold, p = 0.09, Figure 3B). [score:4]
For example, IGFBP5 is a positive regulator of IGF1 (also target of miR-206, Table 2) signalling and both are severely reduced in ALS muscle [71]. [score:4]
Abbreviations: M, males; F, females; p(PX), p-value at indicated postnatal day X. In SOD1-G93A males, no changes in any of the studied miRNA were found at P10, P40 or P60, although suggestive but non-significant upregulation of miR-206 was observed at P60 in EDL (Figure 2A, 1.7 fold, p = 0.10) and plasma (Figure 2B, 3.8 fold, p = 0.10). [score:4]
However, the release or secretion of miRNAs from the muscle tissue to the circulation, including that of miR-206, may be a regulated process that requires uncompromised muscle function which is lost at the terminal disease stage (between P100 and P120). [score:4]
Increase in circulating myomirs miR-1, miR-133a, miR-133b and miR-206 have been demonstrated in various mo dels of striated muscle pathologies [41], [53], [57] whereas they are frequently downregulated in cancer [58]. [score:4]
Indeed, plasma miR-206 was upregulated 23.5 fold (p<0.00001, Figure 2C) at this age. [score:4]
Abbreviations: M, males; F, females; p(PX), p-value at indicated postnatal day X. In SOD1-G93A males, no changes in any of the studied miRNA were found at P10, P40 or P60, although suggestive but non-significant upregulation of miR-206 was observed at P60 in EDL (Figure 2A, 1.7 fold, p = 0.10) and plasma (Figure 2B, 3.8 fold, p = 0.10). [score:4]
Sufficiently high levels of expression was found only in 10 miRNAs: miR-133a, miR-206, miR-1, miR-145, miR-24, miR-19b, miR-17, miR-106b, miR-20a and miR-21. [score:3]
B) Relative miR-206 expression in male SOD1-G93A plasma. [score:3]
A) Relative miR-206 expression in male SOD1-G93A muscles at various stages of the pathology (P10– P120). [score:3]
Among the thousands of miR-206 target transcripts predicted by various bioinformatics tools [69] more than 50 are experimentally validated (Table 2). [score:3]
Briefly, the only miRNA whose expression was increased consistently at any stage/tissue/sex was miR-206. [score:3]
B) Relative miR-206 expression in female SOD1-G93A plasma. [score:3]
This may indicate pathological induction of miR-206 in the neuronal or associated cells where it is not normally expressed. [score:3]
miR-206 is also elevated in the nervous system in various pathological conditions including Alzheimer’s disease and cerebral ischemia [63], [64], in schizophrenia [65], as well as in cytotoxic insult upon exposure to environmental toxin [66]. [score:3]
Experimentally verified targets for miR-206. [score:3]
C) Relative miR-206 expression in SOD1-G93A plasma from symptomatic animals at postnatal day 100. [score:3]
A) Relative miR-206 expression in female SOD1-G93A muscles at various stages of the pathology (P60– P120). [score:3]
0089065.g002 Figure 2A) Relative miR-206 expression in male SOD1-G93A muscles at various stages of the pathology (P10– P120). [score:3]
0089065.g003 Figure 3A) Relative miR-206 expression in female SOD1-G93A muscles at various stages of the pathology (P60– P120). [score:3]
miR-206 and miR-133b are clustered, and their co -expression as bicistronic transcript in myogenic conversion in vitro and in denervation in vivo has been documented [44], [50]. [score:3]
miR-206 and miR-106b are elevated in the circulation of ALS patients. [score:1]
The most outstanding result is that levels of miR-206, which is known to be involved in the maintenance of neuromuscular connectivity in ALS mice [44], are elevated not only in the affected muscle of both male and female SOD1-G93A mice but also in the blood plasma of these animals and in serum samples from human ALS patients. [score:1]
miR-206 is elevated in fast-twitch muscle and circulation of SOD1-G93A females. [score:1]
Deletion of miR-206 in vivo does not lead to muscle atrophy or alterations in NMJ maturation. [score:1]
Furthermore, although miR-206 levels in male EDL muscle progressively increased towards the terminal stage (Figure 2A), its circulating levels (Figure 2B) were decreased at the terminal stage where muscles are severely atrophic. [score:1]
Besides the protective role of miR-206 in SOD1-G93A mo del, its other potential functions in ALS remain unknown. [score:1]
Therefore, it may be plausible that miR-206 (and miR-106b) can be used in the future to screen potential candidate drugs or treatments for ALS. [score:1]
Like in males, miR-206 was unaffected in SOL (Figure 3A, bars with diagonal stripes). [score:1]
When all ages are combined, the only consistently altered miRNA in the course of ALS pathology in SOD1-G93A mice was miR-206. [score:1]
The data indicates that muscle-enriched miR-206 may serve as a non-invasive circulating biomarker for ALS, and warrants larger scale studies on SALS and FALS patients. [score:1]
Because it remained possible that the peak elevation in circulating miR-206 has been missed between the age groups P90 and P120, miR-206 was further studied from male mice at the age of 100–105 days (mean 102 days in controls and 101.9 days in mutants). [score:1]
In this mo del, the elevated circulating levels of miR-1, miR-133a and miR-206 show dose-responsive restoration to wild type levels in response to exon-skipping therapy that restores dystrophin levels. [score:1]
miR-206 was unaffected in slow SOL muscle at P90 or P120 (Figure 2A, bars with diagonal stripes). [score:1]
The two miRNAs found to be elevated here, miR-206 and miR-106b, may provide ideal biomarkers as they can be sampled from blood. [score:1]
miR-206 is elevated in fast-twitch muscle and circulation of SOD1-G93A males. [score:1]
Albeit the relative levels of miR-206 in male EDL increased progressively towards the end stage, the circulating miR-206 dropped dramatically from the onset of symptoms to the terminal stage (Figures 2A and 2B). [score:1]
Elevated circulating miR-206 levels were detected in both sexes of SOD1-G93A mice, although the level and age at which this occurred differed according to the symptomatic onset (males are affected earlier in this mo del). [score:1]
At P120, miR-206 was 4.2 fold up in female EDL (p = 0.03) to the same extent in circulating plasma (p = 0.02). [score:1]
Abbreviations: LUC, luciferase assay; WB, western blot; qPCR, quantitative PCR; NB, northern blot; HEK293, human embryonic kidney cells; NIH10T1/2, fibroblasts; MCF-7, breast cancer cell line; MDA-MB-231, human adenocarcinoma cells; miR-206- KO,miR-206 knockout mouse; PASMC, pulmonary artery smooth muscle cells; HMEC, human mammary epithelial cells; RK3E, rat kidney cells; MCF10A, mammary epithelial cells; NIH3T3, mouse embryonic fibroblast cells; DF1, chicken embryonic fibroblasts; U343, human glioma cells; SK-N-SH, human neuroblastoma cells; C2C12, immortalized mouse skeletal myoblasts; SMSC, mouse skeletal muscle satellite cells; RuGli, rat glioma cells; COS7, African green monkey kidney cells; AML12, mouse hepatocytes; RMS, rhabdomyosarcoma cells; GC, human gastric cancer cells; HEK293T, human embryonic kidney cells with SV40 Large T-antigen; N2a, mouse neuroblastoma cells; SH-SY5Y, human neuroblastoma cells; MEF, mouse embryonic fibroblasts; MSC, human mesenchymal stem cells; MSC-NC, human mesenchymal stem cell-derived neural cells; HeLa, human epithelial cells from cervical carcinoma; CF, cardiac fibroblasts; CG, rat oligodendrocyte progenitor cells; H441, human lung adenocarcinoma epithelial cells. [score:1]
In conclusion, the increased circulating miR-206 and miR-106b may serve as biomarkers for ALS in humans. [score:1]
[1 to 20 of 55 sentences]
11
[+] score: 161
miR-206 downregulates the expression of c-Met, cycle-related proteins CDK4, and phosphorylated-Rb (p-Rb) in AGS cells. [score:6]
Concurrently, ectopic miR-206 also down-regulated the expression of CDK4, p-Rb, p-Akt and p-ERK. [score:6]
miR-206 downregulated c-Met expression and other cell cycle-related proteins. [score:6]
0128751.g003 Fig 3 miR-206 also downregulates expression of p-Akt and p-ERK1/2, but not total Akt or ERK1/2. [score:6]
miR-206 also downregulates expression of p-Akt and p-ERK1/2, but not total Akt or ERK1/2. [score:6]
c-Met overexpression following miR-206 downregulation seems to be the common etiology for the pathogenesis of gastric cancer in the majority of samples examined in this study. [score:6]
miR-206 expression is associated with weak c-Met expression in gastric tumors. [score:5]
Suppression of miR-206 led to increased c-Met expression in gastric cancer. [score:5]
Conversely, tumors with normal expression of miR-206 showed very weak or negative c-Met expression. [score:5]
miR-206 has previously been shown to inhibit gastric cancer proliferation in part by suppressing cyclin D2 [10]. [score:5]
In the present study, we identified a mechanism for regulation of c-Met gene expression through miR-206 in gastric cancer. [score:4]
We have previously identified c-Met as a direct target of miR-206 [9]. [score:4]
Its promoter is hyper-methylated with elevated levels of miR-206 leading to downregulation of KLF4 [20]. [score:4]
The pre-microRNA expression constructs lenti-miR-206 and pCDH-CMV-MCS-EF1-copGFP control vector were purchased from System Biosciences (Mountain View, CA). [score:3]
Real-time RT-PCR analysis was performed to detect the expression of miR-206 in 40 gastric cancer specimens and normal tissues. [score:3]
*: Differences in cell migration or invasion between miR-206 and negative control transfected cells were significant, P < 0.01. miR-206 can inhibit migration and invasion of AGS cells (Fig 2B and S3 Fig). [score:3]
Restoration of miR-206 leads to G0/G1 cell cycle arrest, confirming its role as a tumor suppressor. [score:3]
Introduction of miR-206 suppressed tumor growth in vivo. [score:3]
Female nude mice, 6 weeks of age, were inoculated with AGS cells (8x10 [6]) expressing miR-206 or negative controls in their flanks, and then sacrificed after 8 weeks. [score:3]
confirmed that c-Met expression was reduced by miR-206 transfection in AGS cells (Fig 3). [score:3]
0128751.g005 Fig 5 of miR-206 in AGS cells suppresses tumor growth in nude mice. [score:3]
c-Met has been predicted and shown to be the target gene of multiple miRNAs including miR-206 [9, 12]. [score:3]
miR-206 is a candidate for both immunohistochemical detection of small tumors and possible target for biological therapeutics. [score:3]
of miR-206 suppressed tumor growth in vivo We next investigated if overexpression of miR-206 could repress tumor growth in vivo. [score:3]
AGS cells were infected with lentivirus expressing miR-206 or negative control. [score:3]
Most tumor samples, with decreased miR-206 expression, showed high percentage (>50%) of c-Met staining. [score:3]
Ectopic miR-206 induces G1 arrest and inhibits cell proliferation, migration and invasion. [score:3]
miR-206 expression was inversely related to the level of c-Met observed in tumor samples (Fig 1B). [score:3]
Although elevated in a few types of cancer including ovarian and Waldenstrom macroglobulinemia, miR-206 is mostly suppressed in solid organ tumors [9]. [score:3]
0128751.g001 Fig 1 (A) Real-time RT-PCR analysis showing the expression of miR-206 in normal tissues (set at 1) and the relative amount of miR-206 in the tumors, as fold reduction. [score:3]
As miR-206 expression was decreased in gastric cancer specimens, we sought to determine whether the introduction of miR-206 had any biological effect on AGS cells. [score:3]
In this study, we were able to confirm that c-Met is significantly involved in gastric cancer and its role as a miR-206 target is pivotal in oncogenesis. [score:3]
*: Differences in cell migration or invasion between miR-206 and negative control transfected cells were significant, P < 0.01. miR-206 can inhibit migration and invasion of AGS cells (Fig 2B and S3 Fig). [score:3]
miR-206 induced G1 arrest and inhibited cell proliferation, migration and invasion of AGS gastric cancer cells. [score:3]
Introduction of miR-206 in AGS cells suppresses tumor growth in nude mice. [score:3]
10 ng of total RNA were used for cDNA synthesis by the Taqman MicroRNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA), and miR-206 expression level was quantified by the Taqman MicroRNA Assay (Applied Biosystems). [score:2]
In vivo tumor growth assayThe pre-microRNA expression constructs lenti-miR-206 and pCDH-CMV-MCS-EF1-copGFP control vector were purchased from System Biosciences (Mountain View, CA). [score:2]
After 8 weeks, the averaged tumor volumes were significantly lower from cells infected with lentivirus expressing miR-206, as compared with control (Fig 5). [score:2]
MicroRNA-206 suppresses gastric cancer cell growth and metastasis. [score:2]
AGS cells transfected with the miR-206 molecule showed inhibition of cell growth as compared to negative control based on the MTS assay (Fig 2A). [score:1]
FACS analysis of AGS cells transfected with miR-206. [score:1]
*: Differences in cell migration or invasion between miR-206 and negative control transfected cells were significant, P < 0.01. [score:1]
The number of colonies was also reduced with transfection of miR-206 (S2 Fig). [score:1]
For each well, 50 nM miR-206 mimics molecule (Ambion, Austin, TX), or a negative control (Ambion) transfection was employed. [score:1]
An inverse correlation was noted between miR-206 and KLF4 in a panel of human colon cancers [20]. [score:1]
S2 Fig AGS cells transfected with miR-206 or NC were seeded at low density. [score:1]
We next investigated if overexpression of miR-206 could repress tumor growth in vivo. [score:1]
A dramatic reduction of migration towards the lower chambers was observed in miR-206 transfected AGS cells (86 ± 15 vs. [score:1]
These findings indicate that miR-206 may not function similarly in all epithelial cells, which negates the one size fits all approach in chemotherapeutics. [score:1]
Although similar findings have been confirmed in gastric, ovarian and breast cancers, the role of miR-206 seems to have an opposite effect in colon cancer [6, 20]. [score:1]
In summary, we demonstrated that miR-206 negatively modulates the c-Met signaling pathway involved in cell proliferation and migration. [score:1]
Based on previous reports, cyclin D2 is elevated in gastric cancer when miR-206 is affected [10]. [score:1]
miR-206 levels in most tissue samples of gastric tumor (34/40) were found to be significantly lower than normal tissues (Fig 1A). [score:1]
S1 Fig AGS cells were collected 48 hours after transfection with miR-206 or NC, stained with propidium iodide, and analyzed by flow cytometry. [score:1]
AGS cells were collected 48 hours after transfection with miR-206 or NC, stained with propidium iodide, and analyzed by flow cytometry. [score:1]
One of the other promising new miRNAs for solid organ tumors includes miR-206 [8]. [score:1]
In addition, cells transfected with miR-206 showed that HGF -induced invasiveness was also significantly hampered following miR-206 transfection (57 ± 12 vs. [score:1]
miR-206 has been shown to be a potent prognostic marker [10]. [score:1]
[1 to 20 of 58 sentences]
12
[+] score: 155
Furthermore, in HeLa cells, miR-206 was reported to promote apoptosis through inhibition of Notch3 expression, thus resulting in inhibition of tumor cell migration [71]. [score:7]
We have also observed that increase in miR-206 expression reflected an increase in cerebral infarct volume while correlating to the downregulation of the Gja1 mRNA (Figure 6B). [score:6]
Proc Natl Acad Sci U S A. 106: 20794– 9. 70 Zhang T, Liu M, Wang C, Lin C, Sun Y, et al (2011) Down-regulation of MiR-206 promotes proliferation and invasion of laryngeal cancer by regulating VEGF expression. [score:6]
We have observed that the expression of miR-206 to be upregulated in the brain of rats subjected to MCAo. [score:6]
284: 31921– 7. 72 Shan ZX, Lin QX, Fu YH, Deng CY, Zhou ZL, et al (2009) Upregulated expression of miR-1/miR-206 in a rat mo del of myocardial infarction. [score:6]
The authors showed that miR-206 participates in the pathogenesis of AD by suppressing Bdnf expression. [score:5]
Although miR-206 is poorly expressed (undetectable level) in normal brains, a high level expression of miR-206 has been observed in AD patients and the AD transgenic mouse mo dels. [score:5]
During the abnormal development of nerve cells, miR-206 affects cell viability and apoptosis, mainly through regulating the expression of Otx2 [80]. [score:5]
miR-206 induced abnormal development of neural cells was considered to be partly mediated via inhibition of orthodenticle homeobox 2 (Otx2) mRNA transcript and translation. [score:5]
In another study, overexpression of miR-206 was found to inhibit the neural cell viability [77]. [score:5]
miR-206 expression peaked at 24 hrs and gradually decreased until 168 hrs while its target, Bdnf exhibited an opposing trend. [score:5]
We have measured miR-206 expression in primary neuronal cells during OGD and found miR-206 expression increased significantly at 4 hrs (relative expression value 1.47±0.09, p<0.05). [score:5]
In myocardial infarction, the upregulated miR-206 induces cell apoptosis via insulin-like growth factor 1 (Igf1) [72]. [score:4]
We could also see correlations with the expression of corresponding mRNAs that are known to be regulated by miR-206 (Figure 6B). [score:4]
Evidently, we observed miR-206 expression increases with increase in infarct volume (Figure 6A). [score:3]
Therefore, it is possible that miR-206 promotes acute cerebral cell death by targeting Cx43 co-operatively with Bdnf, Notch3 and Otx2 (Figure 6B). [score:3]
We observed a positive linear relationship between miR-206 expression and infarct sizes with a Pearson correlation value of R = 0.88 (Figure 6A). [score:3]
miR-206 Expression and Infarct Volume. [score:3]
Another target of miR-206 is the Cx43 (gap junction protein, alpha 1; Gja1), a primary component of gap junction proteins, the intercellular channels in astrocytes. [score:3]
rno-miR-206, -21*, -290, -291a-5p, -300-5p, -30c-1*, -503, -542-5p, -874 and -877 increased in expression from 0 hrs to 24 hrs and gradually decreased from 48 hrs to 168 hrs. [score:3]
Overexpression of miR-206 in cultured primary mouse hippocampal neurons resulted in a decrease in the dendritic spines density. [score:3]
We found that miR-206 expression increased significantly (p<0.01) when 30 nM miR-206 mimic was added to primary neuronal culture during OGD reperfusion. [score:3]
Furthermore, miR-206, miR-290, miR-291-5p and miR-30c-1* expression was found to be positively correlating with the infarct volume. [score:3]
The miR-206 expression decreased significantly (p<0.01) when anti-miR-206 was added (Figure 7A) during the reperfusion incubation period. [score:3]
miR-206 Expression in Primary Neuronal Cells Upon OGD. [score:3]
Target relationship: miR-206/ Bdnf; miR-125b-5p/ Smo; miR-124/ Jag1; miR-146a/ Notch1, Smad4 and Irak1; miR-34a/ Smad4, Jag1 and Wnt3; miR-133b/ Tgfb1; miR-21/ Pdcd4 and Faslg. [score:3]
Among them, expression of rno-miR-206, -290, -291-5p and -30c-1* (Figure 2D) correlated well with the infarct volumes with R values of 0.96, 0.95, 0.97 and 0.95 respectively. [score:3]
The expression of miR-206 positively correlated with infarct volume expansion in the eMCAo mo del. [score:3]
Subsequently, Leivonen et al [76] have demonstrated that miR-206 could target estrogen receptor-α and repress estrogen receptor-α responsive gene. [score:3]
Expression of Gja1 (p<0.05), Otx2 (p<0.01) and Bdnf (p<0.01) significantly increased in neuronal cells that were transfected with anti-miR-206 during reperfusion period. [score:3]
Hence, the level of miR-206 expression could be used in determining the progression of recovery or specifically the reduction in infarct volume. [score:3]
Inhibitor (anti) or miR-206 mimic at 30 nM each (final) in 50 µl of Opti-MEM was complexed with 1 µl of NeoFx in 50 µl of Opti-MEM (Ambion, Inc, USA). [score:3]
0066393.g007 Figure 7(A) miR-206 expression is significantly increased in the presence of miR-206 mimic (p<0.01) and significantly decreased when cells were transfected with anti-miR-206 (p<0.01) during reperfusion. [score:3]
We also observed that anti-miR-206 could reduce neuronal cell death significantly (Figure 7B, 7C) along with significant increase in Gja1, Otx2 and Bdnf expression (Figure 7D). [score:3]
Cell viability and corresponding gene expression in primary neuronal culture transfected with anti-miR-206 or miR-206 mimic during reperfusion following OGD. [score:3]
From our profiling data, we also observe that miRNA families such as miR-206/−133b; miR-200a/−141; miR-34a/−449a; miR-17-5p/−18a may be working together to regulate neuronal repair mechanisms. [score:2]
0066393.g006 Figure 6(A) MiR-206 expression as validated by qRT-PCR in an independent cohort of eMCAo mo dels with varying infarct sizes. [score:2]
miR-206, is a muscle-specific miRNA and is a key regulator of muscle cells proliferation, differentiation, apoptosis, migration and angiogenesis [51], [67]– [70]. [score:2]
Our study also highlights that the miRNAs such as miR-206 could be involved in recovery processes to bring about a favorable outcome in cerebral ischemia. [score:1]
Neuronal cell death following OGD is significantly reduced by anti-miR-206 that was added during reperfusion period. [score:1]
We measured the miR-206 expression in eMCAo brain samples that were randomly selected at different time points from an independent cohort with varying infarct sizes (averaging from 50 mm [3] to 380 mm [3]) by quantitative PCR. [score:1]
A206 denotes anti-miR-206; P206 indicates pre-miR-206. [score:1]
miR-206 and Cerebral Ischemia. [score:1]
Cells subjected to OGD (and/or anti/miR-206 mimic) were stained with Hoechst 33342 and Ethidium Homodimer III (EtHD) dye as per the manufacturer’s protocol (Biotium, USA. [score:1]
Reduction in both miR-206 and infarct volume was observed when the rats subjected to MCAo were administered with MK-801 and PLA [2,] to reverse the ischemic brain injury [10]. [score:1]
In contrast, increased cell death was observed when miR-206 mimic was added during the reperfusion. [score:1]
miR-206 correlated with increased cell death in vivo. [score:1]
The authors further demonstrated that intranasal delivery of miR-206 antagomiR improved memory function and increased Bdnf levels, while the intracerebral injection of the antagomiR enhanced the memory function, increased synaptic density and neurogenesis in AD (Tg2576) mice. [score:1]
Inverse correlation was observed between miR-206 and Bdnf, Notch3, Otx2 and Gja1. [score:1]
In this study we could demonstrate the correlation between miR-206 and infarct volume. [score:1]
[1 to 20 of 50 sentences]
13
[+] score: 146
Other miRNAs from this paper: hsa-mir-205, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-133b
In addition, we find that knockdown of Malat1 inhibits KRAS and ANXA2 expression, and that this can be reversed by co-transfection of miR-206 inhibitor. [score:8]
On the other hand, overexpression of miR-206 suppressed Malat1 expression, suggesting that Malat1 is in turn negatively regulated by miR- 206. [score:8]
Knockdown of Malat1 inhibits expression of miR-206 targeting ANXA2 and KRAS. [score:8]
MicroRNA-206 (miR-206) belongs to the group of so-called “myomiRs” [10] and is downregulated [11, 12, 13, 14] or upregulated [15, 16, 17] in various types of cancer. [score:7]
Malat1 knockdown upregulated miR-206 expression. [score:7]
The sponging of miR-206 by Malat1 overexpression has oncogenic effects since miR-206 is no longer able to suppress downstream targets ANXA2 and KRAS, which are involved in GBC progression. [score:7]
MiR-206, a tumor suppressor gene in various types cancer [19], was chosen for further studies given its high upregulation (fold change = 2.78) in response to Malat1 knockdown in NOZ cells compared to the scrambled control (Figure 2C). [score:5]
Moreover, miR-206 inhibitor increased Malat1 levels in NOZ cells while miR-206 mimic decreased Malat1 expression (Figure 2F). [score:5]
The percentage of NOZ cells in S-phase decreased after Malat1 siRNA transfection, while the reduction of expression was rescued by co-transfection of miRNA-206 inhibitor. [score:5]
MiR-206 has been reported as a tumor suppressor gene in human pancreatic ductal adenocarcinoma (PDAC), directly targeting oncogenes KRAS and annexin a2 (ANXA2) [23]. [score:5]
However, this inhibition was attenuated by co-transfection of miR-206 inhibitor (Figure 4A, 4C, 4D, 4F). [score:5]
Figure 5(A) Cell cycle phase determination and (B) corresponding statistical summary, (C) cell apoptosis and (D) corresponding statistical summary, in NOZ cells transfected with si-NC, si-Malat1, miR-206 inhibitor, miR-206 inhibitor+si-Malat1, si-ANXA2 and si-KRAS. [score:5]
Malat1 inhibits expression of endogenous miR-206 and increases levels of ANXA2 and KRAS. [score:5]
Figure 4The mRNA level of (A) ANXA2 and (B) KRAS, and protein levels of (C) ANXA2 and KRAS in four groups of NOZ cells: si-NC, si-Malat1, miR-206 inhibitor, and miR-206 inhibitor+si-Malat1. [score:5]
The mRNA level of (D) ANXA2 and (E) KRAS, and protein levels of (F) ANXA2 and KRAS in four groups of GBC-SD cells: si-NC, si-Malat1, miR-206 inhibitor, and miR-206 inhibitor+si-Malat1. [score:5]
The mRNA level of (A) ANXA2 and (B) KRAS, and protein levels of (C) ANXA2 and KRAS in four groups of NOZ cells: si-NC, si-Malat1, miR-206 inhibitor, and miR-206 inhibitor+si-Malat1. [score:5]
Similarly, we found that miR-206 is downregulated in GBC. [score:4]
On the other hand, luciferase activity was rescued by miRNA-206 inhibitor in both cases (Figure 3F, 3G). [score:3]
Interestingly, Malat1 expression correlated negatively with miR-206 levels (r = −0.568, P < 0.05) (Figure 2E). [score:3]
Our data suggest that oncogenes KRAS and ANXA2 might be downstream targets of Malat1 and miR-206. [score:3]
In conclusion, our findings suggest that Malat1functions as a competing endogenous RNA to promote KRAS and ANXA2 expression by sponging miR-206. [score:3]
To test whether Malat1 acts as a sponge of miR-206 and promotes ANXA2 and KRAS expression, luciferase reporter plasmids containing the 3′-UTR of ANXA2 and KRAS were constructed (Figure 3E). [score:3]
These results indicate that Malat1 might increase ANXA2 and KRAS by inhibiting miR-206 in GBC. [score:3]
Here we show that Malat1 is overexpressed in GBC tissue and functions as a ceRNA for miR-206. [score:3]
Furthermore, miR-206 was downregulated in GBC tissues compared to match normal tissues (Figure 2D). [score:3]
Dual luciferase reporter assays confirmed that KRAS and ANXA2 can bind miR-206 directly at the “seed site”, which is consistent with previous reports showing that miR-206 targets KRAS and ANXA2 in pancreatic adenocarcinoma [23]. [score:3]
Direct interaction between Malat1/miR-206/KRAS or ANXA2. [score:2]
MiR-206 mimics and inhibitor were transfected into NOZ cells using Lipofectamine TM 2000 (Invitrogen, Carlsbad, CA, USA). [score:2]
Malat1 directly binds to miR-206. [score:2]
These results reveal that Malat1 shares a common miRNA-responsive element with miR-206 and suggest that these molecules play a role in GBC cell proliferation, invasion and apoptosis. [score:1]
The correction between Malat1 and miR-206 in GBC. [score:1]
NOZ cells were transfected with Biotinylated miR-206 or biotinylated mutant miR-206 or biotinylated NC (synthesized by Shanghai Gene Pharma Co, Ltd) using Lipofectamine 2000 according to the manufacturer's instructions. [score:1]
Cell apoptosis was elevated after Malat1 knockdown as measured by anexinV-PI assay, and rescued by miR-206 inhibitor. [score:1]
In addition, we performed pull down experiments using biotin-labeled miR-206 oligos. [score:1]
Two ng of pRL-TK (Promega, Madison, WI, USA) were also co -transfected with miR-206 mimics or miRNA NC into HEK293T cells by using Lipofectamie 2000 (Invitrogen, USA). [score:1]
Moreover, dual luciferase reporter assay also confirmed that Malat1 can bind miR-206 directly. [score:1]
MiR-206 mimic reduced the luciferase activity of pmirGLO-Malat1-wt but not of pmirGLO-Malat1-mut (Figure 3B). [score:1]
Here we used RIP to test whether Malat1 and miR-206 exist in the same RISC. [score:1]
Pearson's correlation coefficient was used to analyze the correlation between Malat1 and miR-206 in cancer tissues. [score:1]
It has been hypothesized that ANXA2 and KRAS might promote turmorigenesis in GBC and play a role downstream of Malat1 and miR-206. [score:1]
On the contrary, relative miR-206 levels were lower in the same GBC cell lines than in H69 cells (Supplementary Figure S1). [score:1]
Furthermore, we performed pull-down experiments by using biotin-labeled miR-206 oligos and found that miR-206 could pull down Malat1. [score:1]
Malat1 was pulled down by biotin-labeled miR-206 oligos, but not the mutated oligos (binding sites were mutated to the complement sequences). [score:1]
[1 to 20 of 43 sentences]
14
[+] score: 142
We transiently co -transfected Hek cells with PGLO-Hmgb3 construct and the relative agonist of miR-206 (mimic-miR-206) (Thermo scientific, Waltham, MA, USA) at a concentration of 25 nM for 48 h. These experiments evidenced down-regulation (32%; p value = 0, 0151) of luciferase expression by co-transfection of Hek cells with PGLO-Hmgb3 and mimic-miR-206 (Figure 6A), confirming the target prediction. [score:8]
In conclusion, a more sensible and specific quantification of miRNAs by absolute Q-PCR analysis highlighted common up-regulation of miR-206, miR-223, miR-199a-5p, miR-199b*, miR-27a, miR-128a, miR-31 and miR-142-5p, and down-regulation of miR-17 in dystrophic fibres isolated from TA, DIA and VA of the adult mdx mouse (Figure S1). [score:7]
Taken together, these data demonstrate that up-regulation of miR-206 upon chronic and acute muscle damage down-regulates Hmgb3 and modifications of the chromatin-status can be speculated as down-stream event. [score:7]
Using a target-gene prediction-analysis with 6 different computational algorithms (PITA, TargetScan, PicTar, ElMMo, miRDb and miRanda), we identified and validated a functional binding site for miR-206 in the 3′ untranslated region (3′UTR) of an X-linked member of a family of sequence-independent chromatin -binding proteins (Hmgb3) [30]. [score:7]
During regeneration of single muscle fibres, Hmgb3 messenger RNA (mRNA) and protein expression was gradually reduced, concurrent with the up-regulation of miR-206. [score:6]
MiR-206 down-regulated the expression of luciferase of 32% (p = 0, 0151) in Hek cells co -transfected with pGLOHmgb3. [score:5]
The same data were obtained when 3T3 cells, which endogenously express Hmgb3 (data not shown), were transfected with mimic-miR-206 (25 nM) for 48 h and the expression level of endogenous Hmgb3 was quantified by qRT-PCR analysis (Figure 6B). [score:5]
Hek cells were co -transfected with PGLO Hmgb3Mut and mimic-miR-206 (25 nM) for 48 h. In these conditions luciferase expression was not significantly down-regulated compared to PGLO-Hmgb3 transfected cells (Figure 6A). [score:5]
MiRNAs were quantified in human muscle fibres of 12 control subjects and 18 DMD patients, confirming the over -expression of miR-17, miR-27a and miR-206 in diseased muscle. [score:5]
The quantification analysis highlighted an opposite expression trend for Hmgb3 and miR-206, further validating inhibition of Hmgb3 by miR-206 (AU = arbitrary units). [score:5]
Absolute quantification confirmed common up-regulation of miR-206, miR-199a-5p, miR-223 and miR-199b* in all mdx single fibres tested (Figure S1). [score:4]
MiR-206, miR-31, miR-21, miR-335-5p, miR-27a, miR-142-5p and miR-223 were significantly up-regulated afterwards muscle damage respect damaged muscle. [score:4]
In the case of the FRG1 over -expressing mice, only 4 of the tested miRNAs were found over-expressed in all muscle analyzed (miR-206, miR-223, miR-199a-5p and miR-199b), while the remaining 10 miRNAs showed a heterogeneous behaviour depending on the muscle considered. [score:4]
Instead no down-regulation happened when the binding site of miR-206 was mutated. [score:4]
Moreover the up-regulation of miR-206, which is a myomiR associated to muscle regeneration, was confirmed in human dystrophic fibres as already demonstrated by Greco et al [16]. [score:4]
These experiments evidenced opposite expression profiles of Hmgb3 and miR-206 during myogenesis. [score:3]
New Muscular miRNAs and miRNA-206 are Over-expressed in DMD Patients. [score:3]
Data obtained confirmed over -expression of miR-17, miR-27a and miR-206 in single fibres of DMD muscle biopsies (Figure 4B and 4C). [score:3]
More importantly, miRNAs recently associated to muscle regeneration such as miR-31, miR-206 and miR-335-5p were confirmed over-expressed after acute damage [16]. [score:3]
Dystrophic muscle fibres isolated from different animal mo del of MDs were commonly characterized by the over -expression of several miRNAs (miR-15b, miR-21, miR-27a, miR-31, miR-128a, miR-142-5p, miR-199a-5p, miR-199b, miR199b*, miR-206, miR-221, miR-223 and miR-335-5p) with an expression profile strictly dependent on muscle impairment and damage accumulation (Figure 7). [score:3]
Moreover, two further miRNAs were quantified in human dystrophic fibres: miR-15b, whose over -expression was formerly observed in the mdx mouse by Cacchiarelli et al. [17] but not in DMD muscle [15]; and miR-206, whose expression profile was wi dely investigated in dystrophic and damaged muscle with controversial results [15], [16], [17], [34], [40]. [score:3]
Single muscle fibres were dissected from the muscle biopsies of 12 healthy subjects and 18 DMD patients with an age range between 1 and 18 y-o (Figure 4A), and expression levels of miR-15b, miR-17, miR-27a, miR-128a and miR-206 were quantified by absolute Q-PCR analyses. [score:3]
Data obtained evidenced a group of miRNAs whose expression does not change during muscle repair afterwards acute damage (miR-15b, miR-17, miR-128a, miR-221, miR-199a-5p miR-199b and miR-199b*) (Table 1), and a group of miRNAs that are triggered afterwards CTX delivery (miR-206, miR-31, miR-21, miR-335-5p, miR-27a, miR-142-5p and miR-223) (Table 1), suggesting major involvement of the latter in muscle regeneration. [score:3]
Figure S3 Expression and localization of miR-206 in damaged and dystrophic muscle. [score:3]
These data are also in agreement with previous works describing several target genes of miR-206 such as the Connexin43, DNApolI, Utrophin and Pax7 during muscle regeneration [41], [42], [43], [44]. [score:3]
We identify fourteen miRNAs associated to dystrophic fibres (miR-15b, miR-17, miR-21, miR-27a, miR-31, miR-128a, miR-142-5p, miR-199a-5p, miR-199b, miR199b*, miR-206, miR-221, miR-223 and miR-335-5p) that may mediate muscle regeneration and remo delling in animal mo dels of MDs and acute muscle damage, and confirm over -expression of the previously identified regeneration -associated myomiR-206. [score:3]
The expression levels of miR-21, miR-142-5p, miR-199a-5p, miR-199b*, miR-206, miR-223 and miR-335-5p were instead strictly related to the type of muscle considered, underling a relationship with muscle-type dependent impairment (Figure 2B). [score:2]
To further verify the role of Hmgb3 in myogenesis, we quantified and compared Hmgb3 transcript and miR-206 expression in proliferating C [2]C [12] myoblasts (MB) versus differentiated C [2]C [12] myotubes (MT) obtained after 7 days of serum-privation (Figure 6D–E). [score:2]
Otherwise, single muscle fibres isolated from lower affected TA and VA of the mdx mouse were respectively associated to 7 (miR-206, miR-199a-5p, mir-223, mir-199b, miR-199b*, miR-21 and miR-221) and 5 (miR-206, miR-199a-5p, mir-223, mir-199b and miR-199b*) dysregulated miRNAs (Figure 1). [score:2]
Nevertheless, specific target genes of Hmgb3 need to be identified in order to more finely characterize the molecular pathway regulated by miR-206 through Hmgb3 upon muscle regeneration. [score:2]
Focusing on the involvement of miRNAs in muscle development and myogenesis, a restricted group of muscle-enriched miRNAs, also called myomiRs (miR-1, miR-133, miR-206 and miR-208), was demonstrated fundamental for muscle physiology and plasticity [9], [10], [11]. [score:2]
Fourteen miRNAs were found dysregulated in dystrophic muscle fibres of the mdx mouse with differences linked to the originating muscle (miR-206, miR-199a-5p, miR-223, miR-199b, miR-199b*, miR-21, miR-221, miR-17, miR-15b, miR-31, miR-128a, miR-142-5p, miR-335-5p and miR-27a). [score:2]
As previously described [17], [34] we demonstrate dysregulation and in situ localization of miR-206 in regenerating single fibres. [score:2]
Following the discovery of miRNAs, their participation was investigated in almost all biological processes and, even more importantly, their central role in gene -expression regulation was implicated in many human diseases [3], [4], [5], [6], [7], [8] Regarding this, in the recent years many efforts were focused to finely characterize the role of miRNAs in myogenesis, so that now the miRNA biogenesis is considered necessary for proper muscle development and a restricted number of miRNAs, known as myomiRs (miR-1, miR-133, miR-181, miR-206, miR-208), is considered as integral part of muscle biology [9], [11]. [score:1]
In particular the potential binding of miR-206 to the 3′UTR of Hmgb3 involves two binding sites (first site goes from nt 575 to nt 585 of Hmgb3-3′ UTR; the second site goes from nt 714 to nt 726 of Hmgb3-3′UTR). [score:1]
H&E staining (C, E, G, I) and miR-206 ISH on serial sections (D, F, H and L) of CTX -injected control TA after day 2 (C, D), 5 (E, F), 7 (G, H) and 10 (I, L) after injury are reported. [score:1]
The cells were transfected with mimic-miR-206 (Thermo scientific, Waltham, Massachusetts) at a final concentration of 25 nM using Lipofectamine2000 (Invitrogen, Life Technologies, Carlsbad, California, USA). [score:1]
Hek Transfection with mimic-miR-206 andHek cells were maintained in DMEM supplemented with 10% FBS and penicillin-streptomycin. [score:1]
In situ hybridization was performed using a locked nucleic acid (LNA) detection probe for mmu-miR-206 (Exiqon, Vedbaek, Denmark), which was labelled with digoxigenin [31] using a DIG oligonucleotide tailing kit (Roche, Milano, Italy). [score:1]
3T3 Transfections with mimic-miR-206. [score:1]
0043464.g006 Figure 6(A) Hek cells were co -transfected with mimic-miR-206 at a concentration of 25 nM for 48 h and with pGLO-control or pGLOHmgb3 or pGLOHmgb3Mut. [score:1]
In situ hybridization analysis showed intense signals of miR-206 in newly formed muscle fibres with centralized nuclei, or regenerating fibres, in both mo dels of muscle damage. [score:1]
H&E staining (A) and miR-206 in situ hybridization (B), performed on serial sections of TA dissected from 3½ months-old mdx mice, are shown. [score:1]
40 McCarthy JJ (2008) MicroRNA-206: the skeletal muscle-specific myomiR Biochim Biophys Acta. [score:1]
Only 7 of the 14 miRNAs associated to dystrophic fibres (miR-206, miR-31, miR-21, miR-335-5p, miR-27a, miR-142-5p and miR-223) were triggered by CTX injury. [score:1]
Hek cells were seeded at 1.3×10 [5] cells per well of a 24-well plate and grown for 20 h. pGLOHmgb3 reporter plasmid or its mutants were co -transfected with mimic-miR-206 (Thermo scientific, Waltham, Massachusetts) at a final concentration of 25 nM using Lipofectamine 2000 (Invitrogen, Life Technologies, Carlsbad, California, USA). [score:1]
The array analysis evidenced a dystrophic miRNA-signature not dependent to the muscle type of origin which include the regeneration -associated miR-206; miR-199a-5p, miR-199b, miR-199b* and miR-223. [score:1]
The only exceptions are represented by miR-206, miR-199a-5p and miR-17 whose dysregulation depended on the muscle considered (Figure 3A). [score:1]
[1 to 20 of 48 sentences]
15
[+] score: 128
org/), has revealed, interestingly, that the miR-1 targets; FOXP1 and HDAC4 have putative target sites for miR-133a or miR-133b, whereas miR-133b target; BCL2L2 also has putative miR-1 or miR-206 target sites. [score:9]
Consistent with these results, miR-206 suppressed the expression of cyclin D1 and phospho-retinoblastoma protein and upregulated p21 and myogenin [62]. [score:8]
Common targets of miR-1 or miR-206 and miR-133a or miR-133b are 538 genes, which is 21.5% of miR-1 or miR-206 targets and 30.6% of miR-133a or miR-133b targets (Additional Table 1). [score:7]
Putative miR-1 or miR-206 targets exist in 2498 genes, and putative miR-133a or miR-133b targets are found in 1756 genes. [score:5]
Ectopic miR-206 expression inhibits cell growth in RMS [46, 52, 62], breast cancer [63, 64], EEC [65] and lung cancer cells [66]. [score:5]
In RMS, low expression levels of miR-206 in tumor tissues were shown to be correlated with poor prognosis for overall survival (n=159), but no difference was found in the expression levels of miR-1 [46]. [score:5]
Figure 5A total of 3716 genes were identified by the TargetScan program as predicted targets of miR-1, miR-133a, miR-133b and miR-206. [score:5]
A total of 3716 genes were identified by the TargetScan program as predicted targets of miR-1, miR-133a, miR-133b and miR-206. [score:5]
Recently, studies from our group and others have shown that downregulation of the miR-1/miR-133a and miR-206/ miR-133b clusters are frequent events in various types of cancer. [score:4]
Except for one report about multiple myeloma [37], studies on miR-1, miR-133a, miR-133b and miR-206 have found them all to be downregulated in many types of cancer (Table 1). [score:4]
To identify the biological processes or pathways potentially regulated by the miR-1/miR-133a and miR-206/miR-133b clusters, we performed GENECODIS analysis [81, 82] with our predicted target list. [score:4]
As mentioned above, although the sequence of each seed region is different, some targets, such as MET, TAGLN2, PNP and LASP1, are commonly regulated by the miR-1/miR-133a and/or miR-206/miR-133b clusters. [score:4]
The total number of genes targeted by miR-1 or miR-206 and miR-133a or miR-133b is 3716. [score:3]
Cell migration and invasion activities are also inhibited by miR-206 in RMS [46, 52, 62], EEC [65] and lung cancer cells [66]. [score:3]
Target genes of miR-206 are MET in RMS [52, 62]; estrogen receptor 1 (ESR1, alias; ERα) in breast cancer [63] and EEC [65]; and notch 3 (NOTCH3) in HeLa cells [80]. [score:3]
Workflow for the bioinformatic analysis of target genes of miR-1, miR-133a, miR-133b and miR-206. [score:3]
The predicted target genes of miR-1 are the same as those of miR-206, and those of miR-133a are the same as those of miR-133b, due to the identical sequences of their seed regions. [score:3]
Several cancers, including PCa, pancreatic cancer, lung cancer, AML, RCC, CRC, BC and thyroid cancer, are among the statistically enriched categories (Additional Table 2), and it is worth mentioning that miR-1, miR-133a, miR-133b and miR-206 are differentially expressed in these types of human malignancies. [score:3]
Similarly, miR-206 expression levels in serum might be used to distinguish RMS from non-RMS tumors (sensitivity of 1.0 and specificity of 0.913) [50]. [score:3]
Aberrant expression of miR-1, miR-133a, miR-133b and miR-206 in cancers. [score:3]
Validated oncogene targets of miR-1, miR-133 and miR-206 in cancers. [score:3]
These targets potentially contribute to specific functional readouts of miR-1, miR-133a, miR-133b and miR-206. [score:3]
Altered expression of miR-1, miR-133a, miR-133b and miR-206 in cancers. [score:3]
In vivo, a tumor suppressive function for miR-206 has been shown in RMS in xenotransplanted mice [62]. [score:3]
miR-206 is similar to miR-1 in terms of expression and function, but its sequence differs from the miR-1 sequence by four nucleotides [26] (Figure 3). [score:3]
miR-1-, miR-133a-, miR-133b- and miR-206-regulated molecular networks in cancers. [score:2]
Conducting qPCR, western blotting, and reporter assays and using bioinformatic prediction programs, recent research has identified several targets of miR-1, miR-133a, miR-133b and miR-206 (Table 2). [score:2]
This bioinformatic analysis indicates that the miR-1/miR-133a and miR-206/miR-133b clusters might supplement each other to regulate several cancer pathways, such as cell growth, cell apoptosis, cell cycle, invasion and angiogenesis (Additional Figure 1). [score:2]
Computational analysis of miR-1-, miR-133a-, miR-133b- and miR-206-regulated molecular networks. [score:2]
As miR-1, miR-133a, miR-133b and miR-206 are mostly downregulated in cancers, gain-of-function experiments are a feasible way to evaluate the functional significance of these miRNAs in various cancers. [score:2]
Gene structure of the human miR-1/133a and miR-206/133b clusters. [score:1]
These facts suggest that miR-1/miR-133a and miR-206/miR-133b clusters might coordinately affect downstream pathways. [score:1]
Moreover, FACS analysis revealed that miR-206 induced apoptosis in RMS [46, 52, 62], EEC [65] and lung cancer cells [66], and induced G0/G1 arrest in RMS [46, 52, 62], breast [63] and lung cancer cells [66]. [score:1]
miR-1-1/miR-133a-2, miR-1-2/miR-133a-1, and miR-206/miR-133b form clusters in three different chromosomal regions in the human genome – 20q13.33, 18q11.2, and 6p12.2, respectively. [score:1]
miR-1-1/miR-133a-2 is in an intron of the C20orf166 gene, miR-1-2/miR-133a-1 is in an intron of the MIB1 gene, and miR-206/133b is in an intergenic region (Figure 2). [score:1]
Alignment of miR-1-1, miR-1-2 and miR-206. [score:1]
Circulating miR-1, miR-133a, miR-133b and miR-206 as potential diagnostic markers. [score:1]
Genes of the miR-1/miR-133a and miR-206/miR-133b clusters. [score:1]
With regard to miR-206, a homologue of miR-1, the articles of its functional role are reported in RMS, breast cancer, endometrial endometorioid carcinoma (EEC) and lung cancer. [score:1]
In RMS cells, miR-206 increased the number of myosin heavy chain (MHC) -positive cells, which means that miR-206 induced myogenic differentiation in RMS cells. [score:1]
Figure 3The structures of precursor miR-1-1, miR-1-2 and miR-206 as constructed by the Mfold program [92] (http://mfold. [score:1]
The structures of precursor miR-1-1, miR-1-2 and miR-206 as constructed by the Mfold program [92] (http://mfold. [score:1]
These high-throughput analyses have found miR-1, miR-133a, miR-133b and miR-206 to be altered in various types of cancers. [score:1]
Functional significance of miR-1, miR-133a, miR-133b and miR-206 in cancers. [score:1]
[1 to 20 of 44 sentences]
16
[+] score: 115
[21]Out of the nine miRNAs that were screened, four were upregulated (miR-135b, miR-155, miR-205 and miR-206: Figure 1a) and five were downregulated (miR-31, miR-148a, miR-181c, miR-200b and miR-210: Figure 1b). [score:7]
[21] Out of the nine miRNAs that were screened, four were upregulated (miR-135b, miR-155, miR-205 and miR-206: Figure 1a) and five were downregulated (miR-31, miR-148a, miR-181c, miR-200b and miR-210: Figure 1b). [score:7]
43, 44, 45 Given that miR-206 is upregulated in the mammary glands of Brca1 conditional knockout mice and in HC11 cells treated with a Brca1 siRNA, and limits the ability of HC11 cell morphogenesis in vitro, we prioritized miR-206 for in vivo analysis to further explore its role in mammary gland development and function. [score:6]
Consistent with this, we also found that the expression of miR-206 was increased in HCC1937 cells, which contain a BRCA1 germline mutation resulting in reduced BRCA1 expression and a truncated BRCA1 protein [32] as compared with the wt BRCA1 control (Figure 1d). [score:5]
To further demonstrate that the reduced luciferase activity is a direct consequence of miR-206 targeting the predicted Sfrp1 3′UTR -binding site, mutations were introduced into the miRNA -binding site. [score:5]
Overexpression of miR-155, miR-205 and miR-206 resulted in a complete loss of HC11 dome formation, whereas, overexpression of miR-135b resulted in an increase in HC11 dome formation (Supplementary Figures 1a and b). [score:5]
55, 70, 71 In conclusion, this work has demonstrated that miR-206 is overexpressed in Brca1 -deficient cells and that overexpression of miR-206, in several ways, mirrors the phenotype in MMTV-Cre Brca1 C o/Co mice. [score:5]
Transgenic mice expressing miR-206 under the control of the MMTV promoter were created and expression was confirmed in mammary glands at day 1 of lactation (Figure 2b). [score:5]
In addition, miR-206 has been shown to regulate Sfrp1 expression during myogenesis in a porcine mo del. [score:4]
[36] Given the role of miR-206 in breast cancer and that it is upregulated in Brca1 loss, it is possible that it may contribute to the consequences of Brca1 loss in the mouse mammary gland. [score:4]
Increased expression of miR-206 did not affect the activity of the mutated Sfrp1 3′UTR (Figure 4d), suggesting that the decrease in luciferase signal can be attributed to the binding of miR-206 to Sfrp1 at the predicted binding site. [score:3]
1, 2, 3, 4, 11 Interestingly, miR-206 overexpression results in defective mammary epithelial differentiation (Figure 2a), in vitro proliferation defects 39, 40, 41 and the induction of apoptosis via the repression of Notch3. [score:3]
To explore this, we first used qRT-PCR to confirm that miR-206 was still overexpressed in the mammary glands of transgenic mice at 12 months of age. [score:3]
[55] To further explore the Brca1-miR-206 pathway, we identified potential gene targets of miR-206 (Figure 4a). [score:3]
miR-206 targets the 3′UTR of the Wingless-type MMTV integration site (Wnt) antagonist, Sfrp1. [score:3]
This demonstrated that out of the four miRNAs assessed, only miR-206 expression was significantly altered (Figure 1c). [score:3]
53, 54, 55 The results revealed that Igf1 was significantly upregulated in the MMTV miR-206 glands as compared with the controls (Figure 3d). [score:3]
[42] These results together with the differential expression data above suggest miR-206 is a strong candidate acting downstream of Brca1. [score:3]
Overexpression of miR-206, decreased the activity of both the Sfrp1 and Notch3 3′UTRs (Figure 4d), confirming that miR-206 can repress both Sfrp1 and Notch3. [score:3]
Interestingly, higher miR-206 expression corresponded to a stronger phenotype, concurrent with this, we found elevated levels of miR-206 in the single control mouse that displayed the phenotype (data not shown). [score:3]
[9] In support of this hypothesis, BRCA1 negatively regulates IGF-1 and loss of BRCA1 is associated with an increase in IGF-1. [52] A plausible hypothesis is therefore that loss of Brca1 causes an increase in miR-206, which in turn results in tissue remo deling in older mice and that this permits Brca1 -associated tumor development. [score:3]
[35]The expression of miR-206 was also evaluated in mouse mammary epithelial tissue at various stages of the mammary gland development (virgin, pregnant, lactating and involution). [score:2]
Although we focused on miR-206, our data concur with other reports in suggesting other miRNAs, such as miR-155, [29] can regulate downstream functions of Brca1, highlighting that this and other miRNAs are an important facet of Brca1 biology and function. [score:2]
To determine whether miR-206 could repress the Sfrp1 3′UTR in mice, a luciferase reporter assay was conducted with the Notch 3′UTR, a known target of miR-206, as a positive control. [score:2]
Another team demonstrated that the knockout of Sfrp1 in mice mammary glands promotes precocious mammary gland development with branching and alveolar development characteristic of the midpregnant mammary gland, 68, 69 a feature that has not been observed in the MMTV miR-206 mice (Figure 3a). [score:2]
The expression of miR-200c, another epithelial marker, was found to be significantly decreased in MMTV miR-206 glands as compared with the controls, further corroborating the β-catenin staining (Figure 3c). [score:2]
We therefore decided to further explore the role of miR-206 in mammary gland development. [score:2]
[35] The expression of miR-206 was also evaluated in mouse mammary epithelial tissue at various stages of the mammary gland development (virgin, pregnant, lactating and involution). [score:2]
[46]In contrast, MMTV miR-206 transgenic mice at 12–15 months of age displayed a striking mammary phenotype. [score:1]
This raises the possibility that miR-206 contributes to the effects of Brca1 loss in the mammary gland and that this likely involves the Wnt pathway through Sfrp1 and the Igf pathways. [score:1]
There are several potential molecular and cellular mechanisms for the observed phenotype, including a miR-206 -associated increase in epithelial cell apoptosis, epithelial to mesenchymal transition, induction of IGF and/or adipose production. [score:1]
This supports the hypothesis that the Igf1 pathway may contribute to the phenotype in MMTV-miR-206 mouse mammary glands. [score:1]
MMTV-miR-206 mice show a defect in mammary gland structure after 12 months. [score:1]
[50] Although the proposed expansion of the stromal compartment may promote tumorigenesis, no tumors were detected in the mammary glands of MMTV-miR-206 glands. [score:1]
Though, there are conflicting reports of Sfrp1 function in the mammary gland, a recent study has shown that Sfrp1 deficiency induces increased adiposity upon forced weight gain in mice, consistent with our observations in aged MMTV miR-206 mice. [score:1]
A role for miR-155, miR-205 and miR-206 in mammary epithelial morphogenesis is consistent with previous studies in other epithelial cell types. [score:1]
miR-206 levels were highest in virgin animals as compared with the other stages of mammary gland development (Figure 1e). [score:1]
[46] In contrast, MMTV miR-206 transgenic mice at 12–15 months of age displayed a striking mammary phenotype. [score:1]
[67]A miR-206 -binding site was identified in the Sfrp1 3′UTR and shown to be evolutionary conserved (Figure 4c). [score:1]
[67] A miR-206 -binding site was identified in the Sfrp1 3′UTR and shown to be evolutionary conserved (Figure 4c). [score:1]
This suggests either that miR-206 has no role in these processes or that any affect is masked by increased branching morphogenesis induced by the various hormonal cascades during pregnancy and lactation. [score:1]
[50]Although the proposed expansion of the stromal compartment may promote tumorigenesis, no tumors were detected in the mammary glands of MMTV-miR-206 glands. [score:1]
To explore the possibility that the IGF-1 pathway may also contribute to the phenotype in miR-206 mice, the expression of Igf1 was evaluated and normalized against the total volume of epithelial cells using miR-200c. [score:1]
[1 to 20 of 43 sentences]
17
[+] score: 109
This study describes how p19 affects the RNA world and shows that: i) miR-342, miR-206, miR-330, miR-138 and miR-99b are upregulated by p19 but not by p19W164A mutant; ii) anti-miR-206 can restore the G2 phase in the presence of p19; iii) p19 and p21Q61L regulate their own alternative splicing; iv) miR-206 and miR-138 are differentially regulated by p19 and p21 H-Ras and v) P19G12S Costello mutants show a clear upregulation of miR-374, miR-126, miR-342, miR-330, miR-335 and let-7. These results allow us to conclude that the H-Ras G12S mutation plays an important role in miRNA expression and open up a new line of study to understand the consequences of this mutation on Costello syndrome. [score:13]
Additionally, we have shown that miR-206 is regulated by the alternative splicing of H-Ras (Fig.   3a) as the ovexpression of p19 upregulates miR-206 more effectively than p21 H-Ras when pEGPP-19 and pEGPP-21 are stably expressed in KO H-Ras [(−/−)]. [score:9]
We analyzed the obtained miRNAs by the TARGETSCAN tool and observed that miR-330 may target SC-35 and many other SR proteins as well as an UsnRNP core protein, mir-342 may target SF4, and miR-206 may target p68 RNA helicase and many other SR proteins. [score:9]
Adams et al. have indentified ERα as a direct miR-206 target, and further demonstrated that miR-206 inhibited the mRNA and protein expression of ERα in human ovarian cells [32]. [score:8]
miR-206 has been reported to be the miRNA whose expression is most downregulated in metastatic cells and has also been shown to regulate cell migration and morphology [23]. [score:7]
These latter results have driven us to further study the regulation of miR-206 by H-Ras proteins as overexpression of p19 causes G1/S delay [7] and upregulates miR-206 (Fig.   1a). [score:7]
Figure  1b shows that anti-miR-206 partially antagonizes the effect of p19 on G1/S phases and restores the G2 phase, thus indicating that miR-206 upregulation partially contributes to the G1/S delay observed upon p19 overexpression. [score:6]
Two of the miRNAs upregulated by p19 (Additional file 1) have previously been reported to be of significant interest in cancer studies: miR-342 is one of the miRNA markers for acute promyelocytic leukemia [30, 31] and miR-206 suppresses ERα in breast cancer cell lines and also plays a role in muscular dystrophy [32– 34]. [score:6]
miRNA upregulation by p19 H-Ras was re-validated by RT-PCR with a specific Taqman assay for mature miR-206, miR-342, miR-138 and miR-330 and was found to increase 2-, 1.6-, 16- and 2.5-fold, respectively, upon overexpression of p19 in three independent experiments and quadruplicate analysis. [score:5]
Additionally, expression of miR-206 has been showed to inhibit cellular proliferation and to disturb invasion in ERα–positive endometrial carcinoma cells [37]. [score:5]
As we showed here that miR-206 regulates cell growth (being these observations in agreement with previous published results, see below) we discuss here our a putative protein 3′-UTR target that could be having a role on these cell growth regulation. [score:5]
Herein we have shown that combining p19 overexpression with a miR-206 inhibitor results in a partial decrease of the G1 phase with a clear recovery of the G2 phase, thus indicating that miR-206 is one of the factors contributing to the delay of the G1/S phase. [score:5]
Hela cells line were used in all the experiments stated above P19 alters miRNAs expression but not the cell growth in H-Ras [(−/−)] KO cell linesIn order to further understand how the alternative splicing of H-Ras alters miRNAs, we differentially expressed pEGFP-p19 or pEGFP-p21 in H-Ras [(−/−)] KO MEFs and analyzed their effect on miR-206 and miR-138. [score:5]
Taken together, these findings prompted us to study the contribution of miR-206 upregulation to the G1/S delay, both of which are induced by p19. [score:4]
Hela cells line were used in all the experiments stated above In order to further understand how the alternative splicing of H-Ras alters miRNAs, we differentially expressed pEGFP-p19 or pEGFP-p21 in H-Ras [(−/−)] KO MEFs and analyzed their effect on miR-206 and miR-138. [score:3]
Candidate miRNAs were found to be miR-342, miR-206, miR-330, miR-138, and mirR-99b (Fig.   1a and 1), which vary with p19 but not with the specific p19mut overexpression. [score:3]
Figure  3a shows that p19 has a large effect on miR-206 expression whereas pGFP-p21 increases it only slightly. [score:3]
Fig. 3P19 and p21 H-Ras differentially regulate miR-206 and miR-138. [score:2]
Fig. 1Anti-miR-206 partially antagonizes the effect of p19 on G1/S and G2 phases. [score:1]
The regulation of miR-206 (a) and miR-138 (b) was analyzed in these cells with specific miRNA Taqman assays. [score:1]
miR-335, miR-206 and miR-126 have been shown to significantly reduce the ability of certain cells to metastasize to the lung [23, 35]. [score:1]
b HeLa cells were first transfected with the pSuper-GFP vector containing the sequence of anti-miR-206 and incubated for 2 days under cell-culture conditions. [score:1]
[1 to 20 of 22 sentences]
18
[+] score: 82
Connexin 43 (Cx43), a gap junction channel required in embryonic skeletal muscle, which is also down-regulated during late embryogenesis and early post-natal life was found to be an experimentally verified target of miR-206 and miR-1 during myogenesis [15]. [score:6]
Cell culture experiments have shown that miR-1 and miR-206 promote muscle cell differentiation, whereas miR-133 promotes cell proliferation by down-regulation of different target genes [10, 11]. [score:6]
Although miR-1, miR-133a, miR-133b and miR-206 genes have similar expression patterns, they have different targets and biological functions [4, 10]. [score:5]
miR-1 and miR-133 are highly expressed both in skeletal and cardiac muscles, whereas miR-206 is specifically expressed only in skeletal muscle [10, 11]. [score:5]
Restoration of decreased MyoD levels promotes muscle cell differentiation in vitro and increases miR-1, miR-133a, miR-133b and miR-206 gene expression in human foetal myoblastsForced expression of MyoD in non-muscle cells in culture can induce myogenic differentiation, whereas MyoD -null primary myoblasts exhibited reduced differentiation [26, 27]. [score:5]
Although miR-1, miR-133 and miR-206 are related in terms of expression, they have different targets, biological functions and transcriptional activation [4, 10, 14- 17]. [score:5]
Western blot analysis showed increased levels of HDAC4 (A), a verified target of miR-1, and Connexin 43 (B), a verified target of miR-206 and miR-1 in foetal muscle cells, compared to newborn cells. [score:4]
miR-1, miR-133a, miR-133b and miR-206 are expressed in muscle tissue and induced during muscle cell differentiation, a process that directs myoblasts to differentiate into mature myotubes, which are organized into myofibers. [score:4]
Experiments on adult mouse C2C12 and mouse embryonic fibroblasts showed that MyoD binds to regions upstream of miR-1, miR-133a and miR-206 and regulates their expression [12, 14]. [score:4]
Although miR-1, miR-133a, miR-133b and miR-206 have been extensively studied, there is no information about their expression during the development of human skeletal muscle. [score:4]
There is currently no existing evidence about the expression of miR-1, miR-133a, miR-133b and miR-206 genes during the stages of human muscle development. [score:4]
Although miR-1, miR-133a, miR-133b and miR-206 are well-studied in muscle, there is no information about their expression and function during human development. [score:4]
miR-1, miR-133a, miR-133b and miR-206 were found to be expressed during muscle cell differentiation both in adult primary human myoblasts and adult mouse cell lines [10- 12]. [score:3]
miR-1, miR-133a, miR-133b and miR-206 levels were low in undifferentiated myoblasts, signifying that they are not highly expressed during the stages before differentiation (Figure 2). [score:3]
Ectopic MyoD expression caused an induction of muscle cell differentiation in vitro, accompanied by an increase in the levels of miR-1, miR-133a, miR-133b and miR-206. [score:3]
Restoration of decreased MyoD levels promotes muscle cell differentiation in vitro and increases miR-1, miR-133a, miR-133b and miR-206 gene expression in human foetal myoblasts. [score:3]
presented in this study show that miR-1, miR-133a, miR-133b and miR-206 are induced during human muscle cell differentiation and their levels are increased proportionally to the stage of muscle foetal development. [score:2]
miR-1, miR-133a, miR-133b and miR-206 levels are proportional to the stage of muscle development. [score:2]
A similar observation regarding the increase of muscle-specific miR-206 during mouse embryonic development was recently reported [19]. [score:2]
We examined the levels of miR-1, miR-133a, miR-133b and miR-206 during the development of human foetus. [score:2]
It can be therefore assumed that miR-1, miR-133a, miR-133b and miR-206 levels correlate with the induced in vitro differentiation of myoblasts to myotubes. [score:1]
The purpose of this study was to investigate the expression of miR-1, miR-133a, miR-133b and miR-206 at different stages of the human developing muscle and during differentiation in myoblast cell lines. [score:1]
Among the four miRNAs, miR-1 and miR-206 were found to promote muscle cell differentiation [10, 11]. [score:1]
Of these, the most extensively studied are miR-1, miR-133 and miR-206. [score:1]
These results suggest a mechanism by which MyoD induces in vitro muscle cell differentiation in human foetal cells, accompanied by the induction of miR-1, miR-133a, miR-133b and miR-206 levels in vitro. [score:1]
These results are analogous to the elevated miR-1 and miR-206 levels observed in the newborn muscle cell line in part 3.2 (Figure 2). [score:1]
[1 to 20 of 26 sentences]
19
[+] score: 66
MiR-27b mimic, miR-142 mimic, miR-206 mimic, miR-21 mimic, miR-130a mimic, mimic negative control, miR-27b inhibitor, miR-142 inhibitor, miR-206 inhibitor, miR-21 inhibitor, miR-130a inhibitor, and inhibitor negative control were obtained from RiboBio (Guangzhou, China). [score:13]
Our results indicated that CYP3A activity could be repressed by miR-27b and miR-206 via translational regulation and by miR-142 through transcriptional inhibition of CYP3A4 and CYP3A5. [score:6]
To validate whether miR-27b, miR-206, miR-21, and miR-130a regulate CYP3A4 and miR-27b and miR-142 regulate CYP3A5 by directly targeting binding sites, wild-type and mutant versions of CYP3A4 3′-UTR and CYP3A5 3′-UTR were constructed and cloned downstream of a luciferase reporter gene. [score:6]
These results indicate that miR-206 can functionally target CYP3A4 MRE206 to decrease CYP3A4 expression. [score:5]
LXRα is involved in the basal transcriptional regulation of CYP3A4 in primary human hepatocytes and miR-206 can serve as a negative CYP3A4 regulator by interfering with PXR-activation of CYP3A4 expression 41 42. [score:5]
The CYP3A5 mRNA level was significantly decreased by mimics of miR-27b, miR-142, miR-206 and miR-21, but increased by inhibitor of miR-142. [score:3]
Interindividual differences in CYP3A activity were affected not only by CYP3A4 gene expression but also by miR-27b and miR-206. [score:3]
Although there was no miR-206 binding site in the CYP3A5 mRNA sequence, miR-206 could also repress CYP3A5 gene expression. [score:3]
MiR-206 could repress CYP3A4 gene expression by directly binding with the CYP3A4 3′-UTR, and there by decrease CYP3A activity. [score:3]
The relative level of CYP3A4 mRNA was significantly decreased by mimics of miR-27b, miR-142, miR-206 and miR-130a, compared with negative controls, while the level of CYP3A4 mRNA was increased by inhibitors of miR-27b and miR-142. [score:2]
Our study demonstrated that 35.5% of the interindividual variation in CYP3A activity maybe predicted by CYP3A4 mRNA levels, which are regulated by miR-27b, and miR-206. [score:2]
was significantly decreased by transfection of mimics of miR-27b, miR-206, miR-21, and miR-142 into the human primary hepatocytes, while was significantly increased by inhibitors of miR-27b and miR-206, compared to the control (Fig. 5c). [score:2]
Repressive regulation of CYP3A4 by miR-27b and miR-206. [score:2]
To investigate the effects of miR-27b, miR-206, miR-21, miR-130a and miR-142 on regulation of CYP3A activity, 75 nM mimic or 100 nM inhibitor of miRNA or control was transfected into human primary hepatocytes using Lipofectamine 3000 (Invitrogen Life Technologies, USA). [score:2]
Among the 13 miRNAs studied, miR-27b, miR-206, and miR-21 were significantly negatively correlated with reductions in AT (r = −0.38, P = 0.004, FDR = 0.022; r = −0.42, P = 0.001, FDR = 0.013; r = −0.37, P = 0.005, FDR = 0.022, respectively). [score:1]
The values of activity and mRNA level were measured 48 h after transfection with mimic or inhibitor for miR-206. [score:1]
MiR-27b and miR-206 were also identified to be independent contributors to variability of CYP3A activity in liver tissues. [score:1]
MiR-27b, miR-206, miR-21, miR-27a, and miR-130a were significantly negatively correlated with the formation rates of PAT (r = −0.46, P = 0.001; FDR= 0.013; r =−0.39, P = 0.003, FDR = 0.013; r = −0.35, P = 0.010, FDR= 0.033; r = −0.33, P = 0.014, FDR = 0.036; r = −0.39, P = 0.003, FDR = 0.013, respectively, Supplementary Table S2). [score:1]
MiR-27b, miR-206, and miR-130a were significantly negatively correlated with the formation rates of OAT (r = −0.43, P = 0.001, FDR = 0.013; r = −0.36, P = 0.007, FDR= 0.030; r = −0.36, P = 0.007, FDR = 0.030, respectively). [score:1]
CYP3A4 mRNA, miR-27b, and miR-206 were independent predictors of CYP3A activity, explaining 35.3% of the variance observed. [score:1]
MiR-206 represses CYP3A activity by directly binding with CYP3A4 3′-UTR. [score:1]
Therefore, a total of 13miRNAs, namely miR-21-5p, miR-27a-3p, miR-27b-3p, miR-103a-3p, miR-106a-5p, miR-107, miR-126-5p, miR-130a-3p, miR-142-5p, miR-206, miR-371b-5p, miR-491-3p, and miR-1260b, were selected. [score:1]
Human CYP3A4 3′-UTR fragments, the sequence from 1620 to 2792 (~1173 bp) in the human CYP3A4 mRNA (NM_017460.5), containing a putative miR-27b/miR-206/miR-21/miR-130a binding sites or mutated binding sites (reverse binding sites), and human CYP3A5 3′-UTR fragments, the sequence from 552 to 1105(~554 bp) in the human CYP3A5 mRNA (NM_001190484.2), containing a putative miR-27b/miR-142binding sites or mutated binding sites (reverse binding sites), were cloned into the pmiR-RB-REPORT [TM] Vector (Ribobio Co. [score:1]
[1 to 20 of 23 sentences]
20
[+] score: 60
The significance of the differences in the expression was confirmed for four of the miRNAs, including three down-regulated miRNAs namely miR-181d-5p, miR-140-3p and miR-206 and one up-regulated miRNA namely miR-625-5p) (P < 0.05) (Fig.   2). [score:9]
The significance of the differences in the expression was confirmed for six of the miRNAs, including two down-regulated miRNAs namely miR-181d-5p and miR-206 and four up-regulated miRNA namely miR-1233-3p, miR-183-5p, miR-421 and miR-625-5p) (P < 0.05) (Fig.   3). [score:9]
The significance of the differences in the expression was confirmed for four of the miRNAs, including three down-regulated miRNAs namely miR-181d-5p, miR-140-3p and miR-206 and one up-regulated miRNA namely miR-625-5p (P < 0.05) (Fig.   1). [score:9]
In detail, we selected two miRNAs with high fold changes among the up-regulated (miR-625-5p and miR-183-5p) and four miRNAs with high fold changes among the down-regulated ones (miR-181d-5p, miR-206, miR-142-5p and miR-339-5p). [score:7]
To gain insights into the potential impact of the three validated miRNAs (miR-181d-5p, miR-206 and miR-625-5p) in regulating target genes, we applied miRTargetLink [23]. [score:6]
The RT-qPCR showed the same direction of expression changes as the microarray analysis for six miRNAs namely miR-181d-5p, miR-1233-3p, miR-183-5p, miR-206, miR-421 and miR-625-5p. [score:4]
The RT-qPCR showed the same direction of expression changes as the microarray analysis for five miRNAs namely miR-181d-5p, miR-142-5p, miR-206, miR-339-5p and miR-625-5p. [score:4]
The RT-qPCR showed the same direction of expression changes as the microarray analysis for six miRNAs namely miR-181d-5p, miR-142-5p, miR-1233-3p, miR-206, miR-339-5p and miR-625-5p. [score:4]
Bioinformatics analysis helped to gain insights into the potential impact of the three validated miRNAs (miR-181d-5p, miR-206 and miR-625-5p) on target genes (Additional file 3: Figure S2). [score:3]
Together, the three miRNAs namely miR-181d-5p, miR-206 and miR-625-5p were significantly deregulated in all subgroups of TOF patients. [score:2]
The diagnostic accuracy of only three of the validated miRNAs namely miR-181d-5p, miR-206 and miR-625-5p by ROC analysis was high with AUCs of 0.987, 0.993 and 0.769 respectively in all TOF patients and 0.990, 0.994 and 0.749 respectively in the subset of TOF patients without symptomatic right heart failure. [score:1]
Three miRNAs namely miR-181d-5p, miR-206 and miR-625-5p were validated by RT-qPCR in all TOF groups. [score:1]
These results indicate the high diagnostic accuracy of miR-181d-5p and miR-206 and a moderate accuracy of miR-625-5p in differentiating TOF patients from healthy controls. [score:1]
[1 to 20 of 13 sentences]
21
[+] score: 59
Where no effect of age and/or gender on miR-1 and miR-206 expression was detected (P > 0.05), a significant interaction on miR-1 expression was identified with a Two-Way ANOVA test (P < 0.05). [score:5]
An overall effect of LHRH-agonist treatment was observed for miR-133a and miR-133b expression (P < 0.05), but not in miR-1 or miR-206 expression (P > 0.05). [score:5]
When using Bonferroni multiple comparison post-hoc test it was demonstrated that miR-1 (A), miR-133a (B), and miR-133b (C) expression levels were higher in elderly compared to younger men ([*] P = 0.02, [*] P = 0.03, [***] P = 0.008, respectively) There was no effect of age or gender on mir-206 expression (D) (P > 0.05). [score:4]
In addition, myomiR expression is altered in several mice and human mo dels investigating skeletal muscle atrophy and hypertrophy (Huang et al., 2011; Ringholm et al., 2011) and miR-206 is specifically down-regulated in muscle of patients with Amyotrophic lateral sclerosis (Russell et al., 2012). [score:4]
5α-dihydrotestosterone regulates miR-133a, miR-133b, and miR-206 expression in human primary myocytes. [score:4]
Surprisingly, incubation with 5α-DHT decreased miR-206 (P < 0.05), While MYF-5 was upregulated in response to testosterone or 5α-DHT (P < 0.05), AR, MYOG, and MYOD mRNA was not significantly altered (Figure 5B). [score:4]
miR-1, miR-133a, miR-133b, and miR-206 belong to a group of muscle specific miRNAs (myomiRs) crucial for the regulation of skeletal muscle development and function (Chen et al., 2006; van Rooij et al., 2008). [score:3]
Partly in line with our previous results (Nielsen et al., 2010), a Two-Way ANOVA (RM) demonstrated a main effect of training in terms of decreased expression in all four myomiRs (miR-1, P < 0.0001. miR-133a, P < 0.01. miR-133b, P < 0.0001, miR-206 P < 0.05). [score:3]
miR-206 expression in men was not correlated with testosterone levels or the subjects' maximal oxygen capacity. [score:3]
A Two-Way ANOVA revealed no effect of age, gender or neither any interaction (P > 0.05) on miR-206 expression and therefore no post-hoc test was performed within the gender groups (Figure 1D). [score:3]
miR-1 (E) and miR-206 (H) expression were not correlated with testosterone in men. [score:3]
The expression of mir-1 and mir-206 were identical in skeletal muscle in both castrated and sham operated mice (P > 0.05). [score:3]
Bonferroni multiple comparison post-hoc tests revealed a significant lower expression of mir-133a (B) ([*] P = 0.02) and mir-133b (C) ([*] P = 0.03), but not mir-1 (A) or miR-206 (D) in testosterone blocked patients at rest before training. [score:3]
The expression of mir-1 and mir-206 were not significantly different between castrated and sham operated mice (A). [score:3]
miR-1 and miR-206 expression were not altered by LHRH-agonist treatment before the training period (P > 0.05) (Figures 3A,D). [score:3]
Specific requirements of MRFs for the expression of muscle specific microRNAs, miR-1, miR-206 and miR-133. [score:3]
Five active ARE motifs have been experimentally identified and verified in the promoter region near the co-transcribed miR-206/miR-133b locus (Wyce et al., 2010). [score:1]
Furthermore, it has been shown that miR-133a and miR-206 are lower in skeletal muscle of people with type 2 diabetes (Gallagher et al., 2010). [score:1]
A Two-Way ANOVA (RM) (miR-1, [****] P < 0.0001. miR-133a, [**] P < 0.01. miR-133b, [***] P < 0.001, miR-206 [*] P < 0.05). [score:1]
[1 to 20 of 19 sentences]
22
[+] score: 56
Unexpectedly, while miR-206 and miR-125b were down-regulated in tissue samples, they were up-regulated in plasma samples. [score:7]
However, the expression of miR-206 is down-regulated in some tumor tissue samples, such as breast, gastric and colorectal cancer [14, 43, 44]. [score:6]
The expression of miR-125b has not been consistent so far and the reason of inconsistent expression pattern of miR-206 and miR-125b in tissue and fluid samples remains largely unknown. [score:5]
The expression of miR-150, miR-125b, miR-126* and miR-206 were dysregulated in CRC, which was corresponding to the previous studies but their correlation between tissue samples and plasma samples were weak. [score:4]
A study revealed that miR-206 was down-regulated in CRC tissue samples and was associated with clinical stage, lymph node metastasis and poor survival [14]. [score:4]
The expression of serum miR-206 is significantly higher in rhabdomyosarcoma [41] and in the early stage of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced lung carcinogenesis [42]. [score:3]
The expression levels of miR-375 in tissue and plasma showed significant positive correlation (r = 0.4663, p = 0.0007), while miR-150, miR-125b, miR-126* and miR-206 revealed weak correlation (Table 3). [score:3]
A recent study of miR-206 in melanoma showed that it targeted CDK4, Cyclin C and Cyclin D1 which were cell cycle genes. [score:3]
A comparison between plasma samples of CRC patients and those of healthy controls revealed significant differences in the expression levels of miR-375 (p < 0.0001) and miR-206 (p = 0.0002) (Figure 1). [score:3]
Therefore, miR-206 induced G1 arrest and acted as a tumor suppressor in melanoma [32]. [score:3]
In the plasma samples, the expression levels of either miR-375, miR-206 or the combination of the 2 miRNAs were useful and robust biomarkers for differentiating CRC patients from healthy controls. [score:3]
The results indicated that for plasma sample, miR-375 (p < 0.0001) and miR-206 (p = 0.0002) were dysregulated and could discriminate CRC patients from healthy controls. [score:2]
The search for a possible explanation revealed that miR-206 is a circulating muscle-specific miRNA. [score:1]
To our best knowledge, there are few studies on miR-206 in CRC. [score:1]
The five miRNAs which appeared to have the most potential as biomarkers were miR-375, miR-150, miR-125b, miR-206 and miR-126*. [score:1]
Vickers MM et al. reported that a signature of miR-21, miR-135a, miR-335, miR-206, and let-7a was associated with stage and metastasis [14]. [score:1]
Presently, few reports have been published on circulating miR-206 in CRC. [score:1]
Five of them (miR-375, miR-150, miR-206, miR-125b and miR-126*) were chosen to be validated in plasma and tissue samples. [score:1]
Area under the curve (AUC) was 0.7489 (95% CI: 0.6536-0.8442; p < 0.0001) for miR-375, 0.7053 (95% CI: 0.6122-0.7985; p = 0.0003) for miR-206 and 0.8458 (95% CI: 0.7746-0.9170; p < 0.0001) for the 2 markers together (Figure 3). [score:1]
We screened 5 miRNAs (miR-150, miR-375, miR-125b, miR-206 and miR-126*) which appeared to have the most potential as biomarkers. [score:1]
However, no significant difference was observed in the levels of miR-150 (p = 0.1025), miR-125b (p = 0.1683), miR-126* (p = 0.1631) in plasma samples and miR-206 (p = 0.7061) in tissue samples. [score:1]
However, the mechanisms of miR-206 in CRC remain largely unknown. [score:1]
[1 to 20 of 22 sentences]
23
[+] score: 48
miR-206 expression was reported to inhibit cell proliferation in breast cancer cells (22). [score:5]
Compared with normal human cerebellum, miR-206, 129-5p, and 323-3p expression were found to be downregulated in all MB cell line tested (Figure 3). [score:5]
Insulin appeared in Network 2 as indirectly controlling the expression of miR-206, 324-5p, 432, and 95. miR-323-3p and 495, both belonging to cluster 14q32, were chosen for validation by RT-qPCR. [score:4]
Figure 3 Validation of miR-206, 129-5p, 323-3p, and 495 downregulation by reverse transcriptase-quantitative PCR. [score:4]
Upregulation of miR-206, 129-5p, and 323-3p in DAOY cells. [score:4]
Our miRNA profile (84) Chromosomal localization Fold change Reference DOWNREGULATED hsa-miR-206 6p12.2 −7.53(29) hsa-miR-219-2-3p 9q33.3 −6.64(52) hsa-miR-383 8p22 −6.56(12, 55, 56) hsa-miR-138 16q13.3/3p21.32 −5.16(12, 14) hsa-miR-323-3p 14q32.2 −4.96(12, 52) hsa-miR-122 18q21.31 −4.82 hsa-miR-105 Xq28 −4.66 hsa-miR-129-5p 11p11.2/7q32.1 −4.56(23) hsa-miR-935 19q13.43 −4.53(52) hsa-miR-329 14q32.2 −4.48 hsa-miR-129-3p 11p11.2/7q32.1 −4.43 hsa-miR-650 22q11.21 −4.19 hsa-miR-184 15q24.3 −4.14 hsa-miR-370 14q32.2 −3.99(12) hsa-miR-433 14q32.2 −3.96(29) hsa-miR-138-2* 16q13. [score:4]
Figure 4 Effect of miR-206, 129-5p, and 323-3p overexpression in DAOY cells proliferation. [score:3]
Functional studies using mimic miR-129-5p (11p11.2/7q32.1), miR-206 (6p12.2), and miR-323-3p (14q32.2) and the DAOY cell line, suggested a suppressive role for miR-129-5p in MB proliferation. [score:3]
As expected, miR-206 (p = 0.0001; Mann–Whitney test), miR-129-5p (p = 0.002), miR-323-3p (p = 0.014), and miR-495 (p = 0,054), had lower expression in MB in comparison to normal cerebellum (Figure 3), thus confirming our microarray findings. [score:3]
Expression levels of miR-206, 129-5p, 323-3p, and 495 were performed in MB, normal fetal/newborn cerebellum and four different MB cell lines. [score:3]
As a first approach to investigate the functional significance of miRNAs downregulation in MB, DAOY cells were transiently transfected with mimics of miR-206, 129-5p, 323-3p, or negative control #1. Transfection efficiency was confirmed by RT-qPCR (Figure A2 in). [score:2]
As shown in Figure 4, no consistent differences in proliferation were found in transfections with miR-206 and miR-323-3p. [score:1]
Expression of miR-206, 129-5p, 323-3p, and 495 were also investigated in a representative panel of MB cell lines. [score:1]
No significant differences were found on cell viability or apoptosis after miR-206, miR-129-5p, and miR-323-3p transfections in comparison to control (Figure 4; Figure A3 in, respectively). [score:1]
DAOY cells transfected with miR-206, 129-5p, 323-3p, or scramble mimics were cultured for 24 h in serum-free RPMI-1640 (Cultilab), harvested and part of it was resuspended in the appropriate binding buffer, stained with FITC-conjugated Annexin V (BD Biosciences, San Jose, CA, USA) and propidium iodide at room temperature for 15 min, and subsequently analyzed by flow cytometry in a FACS Canto II (Becton Dickinson). [score:1]
Briefly, mimic-miR-206, mimic-miR-129-5p, and mimic-miR-323-3p or mimic -negative control #1 transfected cells were harvested 20 h after transfection and seeded in triplicate in 96-well plate (1,500 cells/well) in serum-free RPMI-1640 (Cultilab). [score:1]
Transfection of miRVana miRNA mimics (Invitrogen Ambion, Austin, TX, USA) of miR-206, miR-129-5p, miR-323-3p, or miRVana miRNA mimic negative control #1 (referred to as scrambled) was carried out 24 h after seeding, in a final concentration of 3 nM, using Lipofectamine RNAiMAX reagent (Invitrogen) according to the manufacturer’s recommendation. [score:1]
In addition, miR-206 and miR-129-5p were chosen for analysis because of their high fold change (see Table 3), lack of previous functional studies and possible oncogenic role. [score:1]
Mimics for miR-206 and 323-3p had no significant effect on DAOY cells. [score:1]
[1 to 20 of 19 sentences]
24
[+] score: 48
Interestingly, whereas these 4 miRNAs are dramatically up-regulated during myoblasts differentiation [24], they do not have the same expression profile during human muscle development: miR-1 progressively increased during development, miR-133a/miR-133b were highly expressed from 16 weeks of development until birth and miR-206 was expressed at a similar level at all development stages studied (Fig. 1). [score:14]
During the regulation of skeletal muscle development, miR-1 and miR-206 share similar functions, such as their seed sequences, target genes, and muscle-specific expression patterns. [score:7]
The different expression patterns of miR-206 and miR-1 observed during human fetal muscle development suggests a more complex regulation of their expression. [score:7]
This suggests that the D4Z4 contraction does not impact myomiR expression, unlike in Duchenne Muscular Dystrophy (DMD) where miR-1, miR-133a, and miR-206 were highly abundant in the serum of DMD patients but down-regulated in muscle [29, 30]. [score:6]
In contrast, the expression pattern of miR-206 is very similar to what has been reported to occur during mouse embryonic development, where miR-206 was detected at very low levels as early as 9.5 days of development but then increased after secondary muscle fiber formation [26]. [score:5]
However, during the regulation of myogenesis, miR-1 has more regulatory functions when compared with miR-206 since it has more target genes that are able to influence differentiation [27]. [score:4]
Moreover, it has been demonstrated that MyoD and myogenin bind to regions upstream of miR-1 and miR-206, inducing their expression [28]. [score:3]
In muscle cell cultures, miR-1 and miR-206 promote muscle cell differentiation, whereas miR-133 promotes myoblast proliferation [25]. [score:1]
The best-studied myomiRs are the miR-1/miR-206 and miR-133a/miR133-b families. [score:1]
[1 to 20 of 9 sentences]
25
[+] score: 47
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-18a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-26a-1, hsa-mir-99a, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-106a, hsa-mir-107, mmu-let-7g, mmu-let-7i, mmu-mir-99a, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-127, mmu-mir-145a, mmu-mir-146a, mmu-mir-129-1, mmu-mir-206, hsa-mir-129-1, hsa-mir-148a, mmu-mir-122, mmu-mir-143, hsa-mir-139, hsa-mir-221, hsa-mir-222, hsa-mir-223, mmu-let-7d, mmu-mir-106a, hsa-let-7g, hsa-let-7i, hsa-mir-122, hsa-mir-125b-1, hsa-mir-143, hsa-mir-145, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-146a, mmu-mir-148a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-18a, mmu-mir-20a, mmu-mir-21a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-129-2, mmu-mir-103-1, mmu-mir-103-2, rno-let-7d, rno-mir-335, rno-mir-129-2, rno-mir-20a, mmu-mir-107, mmu-mir-17, mmu-mir-139, mmu-mir-223, mmu-mir-26a-2, mmu-mir-221, mmu-mir-222, mmu-mir-125b-1, hsa-mir-26a-2, hsa-mir-335, mmu-mir-335, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-17-1, rno-mir-18a, rno-mir-21, rno-mir-22, rno-mir-26a, rno-mir-99a, rno-mir-101a, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-122, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-126a, rno-mir-127, rno-mir-129-1, rno-mir-139, rno-mir-143, rno-mir-145, rno-mir-146a, rno-mir-206, rno-mir-221, rno-mir-222, rno-mir-223, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, hsa-mir-486-1, hsa-mir-499a, mmu-mir-486a, mmu-mir-20b, rno-mir-20b, rno-mir-499, mmu-mir-499, mmu-mir-708, hsa-mir-708, rno-mir-17-2, rno-mir-708, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-486b, rno-mir-126b, hsa-mir-451b, hsa-mir-499b, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-130c, mmu-mir-21c, mmu-mir-451b, mmu-let-7k, hsa-mir-486-2, mmu-mir-129b, mmu-mir-126b, rno-let-7g, rno-mir-148a, rno-mir-196b-2, rno-mir-486
Further, transfection of MCF-7 human breast cancer cells with an expression plasmid for pre-miR-206 reduced ERα mRNA expression ~ 25%, reduced the basal expression levels of PR, cyclin D1, and pS2 (all well-established ERα-regulated genes), and inhibited cell proliferation with or without E [2] [211]. [score:10]
E [2] Regulation of miRNAs in Human Cell LinesE [2] and the ERα-selective agonist 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) [203] decreased miR-206 expression in MCF-7 cells whereas 2,3-bis(4-hydroxy-phenyl)propionitrile (DPN), an ERβ-selective agonist [204], increased miR-206, pointing to a regulatory loop [162]. [score:5]
The authors of this report called miR-206 a “tumor suppressor” and found that miR-206 was higher in ERα -negative MDA-MB-231 cells [162], offering a mechanism, in addition to ERα promoter methylation [205- 209], for reducing ERα expression in MDA-MB-231 cells. [score:5]
E [2] and the ERα-selective agonist 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) [203] decreased miR-206 expression in MCF-7 cells whereas 2,3-bis(4-hydroxy-phenyl)propionitrile (DPN), an ERβ-selective agonist [204], increased miR-206, pointing to a regulatory loop [162]. [score:4]
The authors suggested that miR-206 may function in a mutually negative feedback loop to temporally regulate ERα expression and ductal/lobuloalveolar proliferation [162]. [score:4]
ERα mRNA stability is negatively regulated by miR-206 in MCF-7 cells and miR-206 expression is higher in ERα negative MDA-MB-231 cells [162]. [score:4]
Surprisingly, Ago2 overexpression in MCF-7 cells increased ERα protein levels by 3-fold, despite also increasing miR-206 that reduces ERα. [score:3]
In contrast the ERβ agonist DPN (10nM) increased miR-206 expression by ~ 60%. [score:3]
Two miR-206 recognition sites were identified in the 3’UTR of ERα and transfection of an expression vector for miR-206 in MCF-7 cells reduced both mRNA and protein levels of ERα [162]. [score:3]
More recent studies showed that miR-206 is inversely correlated with ERα expression, but not ERβ, in human breast tumors [211]. [score:3]
Treatment of MCF-7 cells with 1nM E [2] or the ERα agonist PPT (10nM) reduced miR-206 levels by ~ 80%. [score:1]
More recently, patients whose breast tumors showed reduced miR-126, miR-206, or miR-335 were found to have reduced survival, regardless of ERα or ErbB2 status [18]. [score:1]
Interestingly, miR-206 also reduced β-actin. [score:1]
[1 to 20 of 13 sentences]
26
[+] score: 46
As expected both miRNA are downregulated in a range of cancers, for example miR-1 is downregulated in hepatocellular carcinoma and colorectal cancer [77, 78], while miR-206 is downregulated in gastric and breast cancer [79, 80]. [score:10]
The downregulation of miR-206 in breast cancer is correlated with larger tumor size, but when miR-206 is ectopically overexpressed colony formation and cellular proliferation is inhibited by the prevention of G1 to S cell cycle transition (via the miR-206 target Cyclin D2) [80]. [score:10]
The increased proliferation from cyclin D overexpression is inhibited when miR-206 is upregulated [84]. [score:8]
Mir-1 and its paralog miR-206 are tumor suppressor miRs which are indirectly regulated by NRF2 via HDAC4. [score:5]
Therefore, NRF2 could be indirectly involved in regulating cell proliferation through its association with HDAC4 and miR-206 and ultimately cyclin D1 overexpression. [score:5]
Furthermore, Singh et al identified two miRNA (miR-1 and miR-206) that are indirectly regulated by NRF2 [21]. [score:3]
This is supported by in vivo studies where overexpression of either miR-1 or miR-206 reduced lung cancer growth in nude mice [76]. [score:3]
Similarly gastric cancer is characterised by elevated cyclin D2 levels and low miR-206 expression. [score:1]
miR-1 and miR-206. [score:1]
[1 to 20 of 9 sentences]
27
[+] score: 46
This function of miR-206 is mediated, at least in part, by its target, HDAC4, which inhibits the expression and release of FGFBP1 [61]. [score:7]
Activated by MyoD in activated myoblasts, miR-206 not only can repress Pax3/7 expression, thus further stimulating myoblast activation, but also can repress the p180 subunit of DNA polymerase alpha, whose downregulation coincides with cell cycle exit and differentiation of various tissues [40, 41]. [score:6]
Consistent with its NMJ-specific role, miR-206 deregulation has been associated with the adult motor neuron disease Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease and myotonic dystrophy type 1 (DM1) [61, 62]. [score:6]
Several recent studies profiling miRNA expression in skeletal muscle of young and old mice have revealed that several miRNAs, including miR-206, miR-698, miR-744-5p, and miR-468, are increased, whereas others, such as miR-29, miR-434, miR-455, miR-382, miR-181a, and miR-221, are reduced in skeletal muscle cells of old animals [82– 84]. [score:3]
Others and we have found that the miR-1/206 family, comprised of miR-1-1, miR-1-2, and miR-206, is capable of promoting myogenesis, in part by inhibiting Pax3/7 in embryonic muscle precursors and satellite cells [33– 35]. [score:3]
One miR-206 target, the MET tyrosine-kinase receptor (MET) oncogene, may underlie such functions of miR-206 in RMS [107, 108]. [score:3]
It has been reported that miR-1 and miR-206 levels are repressed in RMS [106], likely resulting in the inhibition of terminal differentiation of myogenic progenitor cells. [score:3]
Conversely, overexpression of miR-206 in RMS cells promotes their terminal differentiation and blocks tumor growth, thus highlighting the important role of miR-206 in RMS pathogenesis. [score:3]
miR-1-1 and miR-1-2 are expressed in both skeletal and cardiac muscles, while miR-206 is specific for skeletal muscle [28, 30, 33, 36]. [score:3]
While both the miR-1/miR-206 family and miR-133 family of miRNAs become enriched in myocytes during differentiation, likely via MyoD- and/or myogenin -dependent transcriptional regulation, their effects and mode of action on myogenesis are different. [score:2]
Lastly, miR-206 has been found to regulate various other muscle-specific genes also important for the maturation of skeletal muscle, including Connexin 43 (CX43), Follistatin-like 1 (Fstl1), and Utrophin (Utrn) [41, 63, 64]. [score:2]
For example, miR-206 is enriched in neuromuscular junctions (NMJs), where it plays important roles in promoting the formation of NMJ endplates [61]. [score:1]
Many MyomiRs and muscle-enriched miRNAs, such as miR-1, miR-133, and miR-206, are all increased in the serum of DMD patients and/or in muscle tissues of mdx mice [89– 96]. [score:1]
Since increased FGF pathway activity is required for NMJ reformation during muscle fiber maturation, removing its repressor HDAC4 locally at NMJs by miR-206 is critical for forming functional skeletal muscle [61]. [score:1]
Linc-MD1 is encoded by a genomic locus that overlaps with the bicistronic miR-206 and miR-133b transcript-coding region [165]. [score:1]
Nevertheless, further studies are needed to definitively establish the role of miR-206 in RMS. [score:1]
[1 to 20 of 16 sentences]
28
[+] score: 41
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-22, hsa-mir-29a, hsa-mir-30a, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-127, mmu-mir-132, mmu-mir-133a-1, mmu-mir-136, mmu-mir-144, mmu-mir-146a, mmu-mir-152, mmu-mir-155, mmu-mir-10b, mmu-mir-185, mmu-mir-190a, mmu-mir-193a, mmu-mir-203, mmu-mir-206, hsa-mir-148a, mmu-mir-143, hsa-mir-10b, hsa-mir-34a, hsa-mir-203a, hsa-mir-215, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-143, hsa-mir-144, hsa-mir-152, hsa-mir-127, hsa-mir-136, hsa-mir-146a, hsa-mir-185, hsa-mir-190a, hsa-mir-193a, mmu-mir-148a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-22, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, mmu-mir-337, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-155, mmu-mir-29b-2, hsa-mir-29c, hsa-mir-34b, hsa-mir-34c, hsa-mir-378a, mmu-mir-378a, hsa-mir-337, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-215, mmu-mir-411, mmu-mir-434, hsa-mir-486-1, hsa-mir-146b, hsa-mir-193b, mmu-mir-486a, mmu-mir-540, hsa-mir-92b, hsa-mir-411, hsa-mir-378d-2, mmu-mir-146b, mmu-mir-193b, mmu-mir-92b, mmu-mir-872, mmu-mir-1b, mmu-mir-3071, mmu-mir-486b, hsa-mir-378b, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, hsa-mir-203b, mmu-mir-3544, hsa-mir-378j, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-let-7k, hsa-mir-486-2
Down-regulated miRNAs Up-regulated target genes mmu-mir-148a ARL6IP1, ARPP19, ATP2A2, CCNA2, CSF1, EGR2, ERLIN1, ERRFI1, FIGF, GADD45A, GMFB, ITGA5, KLF4, KLF6, LIMD2, MAFB, NFYA, PDIA3, PHIP, PPP1R10, PPP1R12A, PTPN14, RAI14, RSBN1L, SERPINE1, SIK1, SLC2A1, TMEM127, TMSB10, TMSB4X mmu-mir-411 APOLD1, SPRY4 mmu-mir-136 RYBP, ARL10, GLIPR2, UGGT1 Up-regulated miRNAs Down-regulated target genes mmu-mir-34a/c DAB2IP, DMWD, EVI5L, FAM107A, MAZ, SPEG, TFRC, TTC19 mmu-mir-92b COL1A2, DAB2IP, G3BP2, HOXC11, LBX1, NFIX, PKDCC, PRKAB2 mmu-mir-132 ACTR3B, AMD1, GPD2, HBEGF, KBTBD13, KCNJ12, PRRT2, SREBF1, TLN2 mmu-mir-146a IRAK1, TLN2 mmu-mir-152 EML2, GPCPD1, NFIX, RPH3AL, SH3KBP1, TFRC, TRAK1, UCP3 mmu-mir-155 DUSP7, G3BP2 mmu-mir-185 DAB2IP, FAM134C, SYNM, TMEM233 mmu-mir-203 APBB2, CACNG7, FKBP5, GDAP1, HBEGF, KCNC1, SIX5, TMEM182 mmu-mir-206 DMPK, G3BP2, GPD2, KCTD13, MKL1, SLC16A3, SPEG mmu-mir-215 KLHL23 Figure 5The network displays the predicted interactions between age-related miRNAs and mRNAs from the sequencing and was generated using Cytoscape (version 3.0, www. [score:17]
Down-regulated miRNAs Up-regulated target genes mmu-mir-148a ARL6IP1, ARPP19, ATP2A2, CCNA2, CSF1, EGR2, ERLIN1, ERRFI1, FIGF, GADD45A, GMFB, ITGA5, KLF4, KLF6, LIMD2, MAFB, NFYA, PDIA3, PHIP, PPP1R10, PPP1R12A, PTPN14, RAI14, RSBN1L, SERPINE1, SIK1, SLC2A1, TMEM127, TMSB10, TMSB4X mmu-mir-411 APOLD1, SPRY4 mmu-mir-136 RYBP, ARL10, GLIPR2, UGGT1 Up-regulated miRNAs Down-regulated target genes mmu-mir-34a/c DAB2IP, DMWD, EVI5L, FAM107A, MAZ, SPEG, TFRC, TTC19 mmu-mir-92b COL1A2, DAB2IP, G3BP2, HOXC11, LBX1, NFIX, PKDCC, PRKAB2 mmu-mir-132 ACTR3B, AMD1, GPD2, HBEGF, KBTBD13, KCNJ12, PRRT2, SREBF1, TLN2 mmu-mir-146a IRAK1, TLN2 mmu-mir-152 EML2, GPCPD1, NFIX, RPH3AL, SH3KBP1, TFRC, TRAK1, UCP3 mmu-mir-155 DUSP7, G3BP2 mmu-mir-185 DAB2IP, FAM134C, SYNM, TMEM233 mmu-mir-203 APBB2, CACNG7, FKBP5, GDAP1, HBEGF, KCNC1, SIX5, TMEM182 mmu-mir-206 DMPK, G3BP2, GPD2, KCTD13, MKL1, SLC16A3, SPEG mmu-mir-215 KLHL23 Figure 5The network displays the predicted interactions between age-related miRNAs and mRNAs from the sequencing and was generated using Cytoscape (version 3.0, www. [score:17]
For example, miR-206 was up-regulated in aged human skeletal muscle, while miR-434 was down-regulated in aged mouse skeletal muscle [10, 12]. [score:7]
[1 to 20 of 3 sentences]
29
[+] score: 40
These findings suggest that the increased miRNA-206 expression levels we observed in T2DM patients may mediate insulin resistance by inhibiting IGF-1 expression. [score:7]
However, although miRNA-206 expression levels were different between T2DM patients and non-diabetic obese individuals, regression analysis revealed that the observed relationship between peripheral insulin sensitivity and miRNA-206 expression was primarily confounded by in vivo mitochondrial capacity and fasting plasma insulin concentrations. [score:5]
miR-206 regulates the growth of the teleost tilapia (Oreochromis niloticus) through the modulation of IGF-1 gene expression. [score:4]
The myomiR miRNA-206 was selected since it was previously reported to be downregulated in gastrocnemius muscle of high-fat diet -induced insulin resistant mice (Chen et al., 2012). [score:4]
Interestingly, a previous study in human subjects indeed reported decreased skeletal muscle miRNA-206 expression upon 12-weeks of endurance training, which was accompanied by increases in mitochondrial capacity and insulin sensitivity (Nielsen et al., 2010), indeed pointing toward a role for miRNA-206 in the regulation of skeletal muscle mitochondrial oxidative capacity, a factor that has been repeatedly demonstrated for its involvement in insulin sensitivity (Hoeks and Schrauwen, 2012). [score:4]
For miRNA-206, all variables but PCrR and FPI were excluded from the mo del (Included variable: PCrR, p = 0.001 and FPI, p = 0.003; excluded variables: BMI, p = 0.57; VO2max, p = 0.89; FPG, p = 0.18; age, p = 0.65; fat %, p = 0.84), indicating that the expression of miRNA-206 is associated with mitochondrial capacity and fasting plasma insulin concentrations. [score:3]
Here, we show that, out of the 25 selected miRNAs, 6 candidate miRNAs (miRNA-133b-3p, miRNA-206, miRNA-27a-3p, miRNA-29a-3p, miRNA-29b-3p, and miRNA-29c-3p) were differently expressed in T2DM patients vs. [score:3]
Figure 2Relative expression levels of miR-133b-3p (A), miR-206-5p (B), miR-27a-3p (C), miR-29a-3p (D), miR-29b-3p (E), and miR-29c-3p (F) in type 2 diabetic subjects (T2DM) vs. [score:3]
Besides obvious differences in species, it should also be noted that all subjects included in this study were weight stable for at least 6 months whereas the mice displaying differences in gene expression of miRNA-206, were in a positive energy balance and were gaining weight on a high-fat diet significantly throughout the study. [score:3]
In contrast to these findings, we show here that miRNA-206 expression was increased in skeletal muscle of T2DM patients as compared to non-diabetic obese/overweight individuals (Figure 2), and that miRNA-206 correlated negatively with peripheral insulin sensitivity (Figure 3). [score:2]
Nonetheless, a possible mechanism linking miRNA-206 to insulin sensitivity is provided by a study demonstrating that reduced miRNA-206 levels increases IGF1 mRNA levels in vivo (Yan et al., 2013). [score:1]
0.83 ± 0.05; p = 0.02), miRNA-206 (2.04 ± 0.23 vs. [score:1]
[1 to 20 of 12 sentences]
30
[+] score: 39
Fusion index was calculated by expressing the number of nuclei within MyHC -positive cells with ≥2 nuclei as a percentage of the total nuclei; n = 4. c SNAIL silencing in RH30 cells upregulates expression of myomiRs, such as miR-1, miR-133b, miR-378a-3p and miR-206. [score:6]
miR-206 inhibits RMS growth by the induction of differentiation [26], and miR-206 induces the expression of MyHC -positive differentiating myoblasts [27]. [score:5]
Muscle-specific microRNAs, such as miR-1, miR-133b, miR-378a-3p, and miR-206 were also upregulated in RH30 shSNAIL cells (Fig.   7c). [score:4]
To verify if miR-206 is a mediator of SNAIL action on MyHC level, RH30 WT cells were transfected with miR-206 precursor (pre-miR-206) and RH30 shSNAIL cells were transfected with miR-206 inhibitor (anti-miR-206). [score:3]
Importantly, in RMS, the SNAIL transcription factor is an important regulator of the MYOD-miR-206-MyHC axis, thereby regulating myogenic differentiation. [score:3]
The results were normalized to U6 snRNA expression level, n = 3. d Transfection of RH30 WT cells with pre-miR-206 induces the MyHC level, whereas transfection of RH30 shSNAIL cells with anti-miR-206 partially restores the effect of SNAIL silencing on the MyHC level. [score:3]
RH30 cells were transfected with the miRNA precursor pre-miR-206 and pre-miR negative control (pre-miR-ctrl), whereas RH30 shSNAIL cells were transfected with miRNA inhibitors: anti-miR-206 or the anti-miR negative control (anti-miR-ctrl). [score:3]
RH30 cells were transfected with 30 nM pre-miR-30a-5p (ID: PM11062, Ambion) or 30 nM pre-miR-206 (ID: PM10409, Ambion) miRNA precursors and pre-miR negative controls (ID: AM17110, Ambion) or alternatively with 30 nM anti-miR miRNA inhibitors against miR-206 (ID: AM10409, Ambion) and negative controls (ID: AM17010, Ambion) using the siPORT NeoFX transfection reagent (Ambion) according to the manufacturer’s instructions, as described previously [41]. [score:3]
Transfection of RH30 WT cells with the miR-206 precursor increased MyHC levels, whereas inhibition of miR-206 with anti-miR sequences in RH30 shSNAIL cells partially reversed the effect of SNAIL on MyHC (Fig.   7d). [score:3]
One of the downstream mediators of MYOD is miR-206 (ref. [score:1]
Those results indicated that miR-206 is a mediator of SNAIL action on MyHC level. [score:1]
U6 snRNA: 5′-CGCAAGGATGACACGCAAATTC-3′ miR-1: 5′-GCTGGAATGTAAAGAAGTATGTATAA 3' miR-133b: 5′-TTTGGTCCCCTTCAACCAGCTA-3′ miR-206: 5′-TGGAATGTAAGGAAGTGTGTGG-3′ miR-378a-3p: 5′-ACTGGACTTGGAGTCAGAAGG-3′ Protein (either nuclear and cytoplasmic fractions or total extracts) was isolated using the Nuclear Extract Kit (Active Motif, La Hulpe Belgium) according to the manufacturer’s protocol. [score:1]
U6 snRNA: 5′-CGCAAGGATGACACGCAAATTC-3′ miR-1: 5′-GCTGGAATGTAAAGAAGTATGTATAA 3' miR-133b: 5′-TTTGGTCCCCTTCAACCAGCTA-3′ miR-206: 5′-TGGAATGTAAGGAAGTGTGTGG-3′ miR-378a-3p: 5′-ACTGGACTTGGAGTCAGAAGG-3′ Protein (either nuclear and cytoplasmic fractions or total extracts) was isolated using the Nuclear Extract Kit (Active Motif, La Hulpe Belgium) according to the manufacturer’s protocol. [score:1]
Kim HK Lee YS Sivaprasad U Malhotra A Dutta A Muscle-specific microRNA miR-206 promotes muscle differentiationJ. [score:1]
An interesting example is miR-206, which is induced by MYOD to enhance differentiation and facilitate cell cycle exit [8]. [score:1]
[1 to 20 of 15 sentences]
31
[+] score: 38
Another recent study of serum obtained from DMD boys demonstrated that in addition to the three myomiRs (miR-1, miR-133a/b, and miR-206) being increased in expression, two other muscle-enriched microRNAs, miR-208b and miR-499 were also increased in expression [37] (Table 1). [score:5]
MyomiRs (a term coined by combining myo/muscle and miR/microRNA) was used to originally describe three microRNAs (miR-1, miR-133a/b, and miR-206) that showed enriched expression in heart and skeletal muscles; but has since expanded from its original definition to include several additional microRNAs that are strongly expressed in muscle lineages [31, 32]. [score:5]
One study generated an AAV overexpressing miR-206 sponge consisting of multimerized miR-206 binding sites, and demonstrated successful inhibition of miR-206 levels following injection into mice [89]. [score:5]
Full transcriptome analysis of microRNAs dysregulated in FSHD myoblasts and serum from FSHD patients revealed a significant increase in expression of the muscle myomiRs (miR-1, miR-133a/b, miR-206) along with significant dysregulation of several other microRNAs [63, 64] (Table 1). [score:5]
MicroRNA expression profiling of the serum from the dystrophic CXMDJ canine dystrophin -deficient mo del also showed a dysregulation of miR-1, miR-133a, and miR-206 [36]. [score:4]
Manipulation of expression of the muscle-enriched microRNAs miR-206 and miR-486 in mouse mo dels of DMD showed benefits in reducing fibrosis, promoting muscle regeneration, and improving overall muscle physiological strength [23, 25]. [score:3]
Follow-up studies in muscles of dystrophin -deficient mdx mice demonstrated that many microRNAs that regulate nNOS signaling, with a particular dysregulation of miR-1, miR-133a/b, and miR-206 (also referred to as “myomiRs”), were significantly altered by the loss of a functional dystrophin protein [29, 30]. [score:3]
The muscle enriched microRNA, miR-206, has been shown to be overexpressed in dystrophic and regenerating skeletal muscle samples along with serum from dystrophic patients and animals [16, 18, 45, 46]. [score:3]
These microRNAs (miR-1, miR-133a/b, and miR-206) were first given the classification as “dystromiRs” as potential diagnostic markers due to their dysregulation in dystrophin -deficient mdx mouse and human DMD patient skeletal muscles [17]. [score:2]
Similar results were observed in dystrophic mdx mouse muscles, which revealed that one particular muscle-enriched microRNA, miR-206, was significantly increased in expression levels when compared with normal mouse muscles [19]. [score:2]
Surprisingly, mice lacking miR-206 showed no overt skeletal muscle or cardiac phenotypes, which has led to the speculation that another microRNA may be playing a compensatory role in its absence [47]. [score:1]
[1 to 20 of 11 sentences]
32
[+] score: 34
Interestingly, phosphorylation of ERK1/2 and AKT downstream effectors were inhibited by restoration of miR-206 in cancer cells, indicating that tumor-suppressive miR-206 inhibited dual signaling networks activated by MET and EGFR. [score:7]
Restoration of mature miR-206 inhibited cancer cell proliferation, migration, and invasion in human lung SCC cell lines through down-regulation of both mRNA and protein levels of MET and EGFR. [score:6]
Overexpression of MET and EGFR and down-regulation of miR-206 were observed in clinical specimens of lung squamous cell carcinoma (SCC) [23]. [score:6]
MiR-206 directly targeted KRAS, thereby acting as tumor suppressor in PDAC cells by blocking cell cycle progression, cell proliferation, migration, and invasion. [score:5]
It has been demonstrated that miR-206 and miR-21 repressed the expression of both RASA1 and SPRED1 by targeting their mRNA 3′-UTRs in triple -negative breast cancer [112]. [score:5]
Re -expression of miR-206 in PDAC cells was sufficient to inhibit tumor blood and lymphatic vessel formation, thus leading to a significant delay of tumor growth and progression. [score:5]
[1 to 20 of 6 sentences]
33
[+] score: 34
Therefore, the observation that expression of these 2 miRNAs behaves differently in response to the same pathological stimuli and that expression of miRNA-23a did not seem to vary between mice, in contrast to miRNA-206, prompted us to suggest that regulation of miRNA-23a expression might be part of a more general process of regulation than the expression of miRNA-206. [score:11]
In our previous study [18], we demonstrated that the expression of miRNA-206 was significantly upregulated in the tibialis anterior muscle of mice undergoing muscular atrophy. [score:6]
This pattern of expression differs from the previously established expression pattern of miRNA-206 in response to muscular atrophy [18]. [score:5]
We provided evidence that expression of miRNA-206 is not constant during development of the disease but rather transient, characterized by strong inter-individual heterogeneity and variability in terms of longitudinal regulation. [score:5]
The miRNA-206 acts as a sensor miRNA, overexpressed in the damaged synaptic regions of muscle fibres of mice where it contributes to the regeneration of presynaptic regions through activation of the HDAC4 and FGFBP1 signalling pathways [51, 52]. [score:3]
As shown (Fig 6A), amongst the 6 miRNAs screened, 15 days after sectioning the sciatic nerve of the mice, miRNA-206 was found to be the most significantly deregulated miRNA. [score:2]
As expected and in line with the quantitative analysis, intense staining of hNIS protein was detected in the pRINES/206T tissues, as a consequence of induction of hNIS protein by miRNA-206, whereas no significant staining was detected in the control pRINES muscle tissues (S1 Fig). [score:1]
These results corroborate well with the now well-established role of miRNA-206 in the regeneration program of skeletal muscle undergoing atrophy. [score:1]
[1 to 20 of 8 sentences]
34
[+] score: 34
Among these upregulated miRNAs were miR-10a, which is a candidate tumor suppressor and suppresses apoptosis in leukemia [39], miR-409 that suppresses tumor cell invasion and metastasis in gastric cancer [40], and miR-206 and miR-345, which are frequently downregulated in various types of cancers and are believed to act as tumor suppressors [41], [42]. [score:15]
As shown in Figure 9C, there was excellent concordance in the data from the miRNA profiling and qPCR, the expression of miR-21, miR-26a, miR-24, miR-30b and miR-29a was down-regulated by EF24 treatment both in vitro and in vivo, while the expression of miR-345, miR-409, miR-10a and miR-206 was upregulated by EF24 treatment. [score:11]
Only four miRNAs (miR-10a, miR-409, miR-206 and miR-345) were upregulated both in vitro and in vivo, which reportedly act as tumor suppressors or inhibitors of cell cycle progression. [score:8]
[1 to 20 of 3 sentences]
35
[+] score: 34
Other work also showed that miR-206 expression was reduced in ERα -positive human breast cancer tissues and that miR-206 suppresses ESR1 expression in addition to inhibiting the growth of MCF-7 breast cancer cells [77]. [score:9]
The miR-206 is upregulated in estrogen receptor negative (ER−) breast cancers and also inhibits the expression of the estrogen receptor gene ERα (ESR1) through two binding sites in the ESR1 3′ UTR [76]. [score:8]
The tumor suppressive role of miR-206 was further confirmed in another study that demonstrated miR-206 to be downregulated in metastatic breast cancer cells in comparison to normal parental cells [78]. [score:6]
Reexpression of miR-206 resulted in reduced invasive capacity and altered cell morphology, which can also limit the migration of metastatic cells. [score:3]
The miR-206 was shown to induce cell cycle arrest and inhibit estrogen -induced proliferation. [score:3]
The miR-206 has been shown to suppress breast cancer migration [74, 75]. [score:3]
These findings suggest a potential role for miR-206 in breast cancer therapy. [score:1]
3.5. miRNA-206. [score:1]
[1 to 20 of 8 sentences]
36
[+] score: 33
Non-infected (Fold-change) miRNA [1] (fold change)MX1 myxovirus (influenza virus) resistance 1 [27]Z23168+11.46gga-miR-155(+3.55)gga-miR-206(−2.86)Interleukin 8 (IL8) [28]M16199+11.03gga-miR-32(+7.98)Interferon regulatory factor 7 (IRF7) [29]U20338+2.11gga-miR-142-5p(+2.84)Interleukin1receptor-like1, transcript variant1 [51]AB041738+1.65gga-miR-460 (only expressed in infected lungs)TNF receptor superfamily, member 19 [30]BX931334−1.85gga-miR-187(−4.35)Tipartite motif-containing 7.1 [52]BX934475−1.81NA [2]RAC serine/threonine-protein kinase3 (ATK3) [53]BX950472−1.65NAC-fringe 1 [54] U97157 −1.52 NANote: [1]miRNAs targeting on differentially expressed immune related genes; [2] No miRNAs targeting on the gene; +: Up-regulated with AIV infection; –: Down- regulated with AIV infection. [score:14]
In addition, three down-regulated miRNAs (miR-206, miR-301 and miR-187) also were predicated to target on AIV genome. [score:6]
Specifically, there was a 2.05 fold up-regulation (7.25 fold in deep sequencing analysis) in miR-451, and 4.71 fold down regulation (2.86 fold in deep sequencing analysis) in miR-206 with AIV infection in lungs (P < 0.05). [score:5]
The expression levels of miR-206 and miR-451 in each sample were measured in terms of threshold cycle value and normalized to U6 expression using 2 [-∆∆CT][48]. [score:3]
Two differentially expressed miRNAs (gga-miR-206 and 451) identified by deep sequencing were confirmed by using TaqMan miRNA assays. [score:2]
There was general consistency between the TaqMan assays and deep sequence analysis of miR-451 and miR-206 in terms of direction of regulation and statistical significance (Figure 3). [score:2]
For example, gga-miR-206 was not identified by DESeq, neither by edgeR, but it was confirmed by real-time RT-PCR. [score:1]
[1 to 20 of 7 sentences]
37
[+] score: 33
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-16-2, hsa-mir-197, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-199a-2, hsa-mir-204, hsa-mir-210, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-138-1, hsa-mir-146a, hsa-mir-193a, hsa-mir-194-1, hsa-mir-195, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34b, hsa-mir-34c, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-363, hsa-mir-365a, hsa-mir-365b, hsa-mir-369, hsa-mir-370, hsa-mir-371a, hsa-mir-375, hsa-mir-378a, hsa-mir-133b, hsa-mir-423, hsa-mir-448, hsa-mir-429, hsa-mir-486-1, hsa-mir-146b, hsa-mir-181d, hsa-mir-520c, hsa-mir-499a, hsa-mir-509-1, hsa-mir-532, hsa-mir-33b, hsa-mir-637, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-509-2, hsa-mir-208b, hsa-mir-509-3, hsa-mir-103b-1, hsa-mir-103b-2, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-371b, hsa-mir-499b, hsa-mir-378j, hsa-mir-486-2
There is evidence that miR-206 plays a key role in the growth and development of the skeletal muscle, promoting the myogenic differentiation and has been related to the pathogenesis of numerous diseases, including heart failure, chronic obstructive pulmonary disease, Alzheimer’s disease, and some cancers [78]. [score:8]
In most of these diseases, miR-206 is downregulated, suggesting this miRNA as a “disease-avoiding” molecule [78]. [score:8]
Moreover, miR-206 suppresses liver X receptor α (LXRα), a gene target of PPAR, thus inhibiting lipogenesis and controlling lipid metabolism in HepG2 cells [80]. [score:7]
miR-206 is specifically expressed in the skeletal muscle, whereas miR-208a is cardio-specific; nevertheless, most of these miRNAs are co-expressed in the heart and skeletal muscles [110]. [score:5]
Interestingly, miR-206 expression is abundant in brown adipocytes in mice but missing in white adipocytes [79]. [score:3]
Interestingly, it has been proven that acute exercise determines an increase in the levels of miR-1, miR-133a, and miR-206 [113], important molecules possibly driving cell-to-cell communication. [score:1]
The myomiRs include miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, miR-486, and miR-499 [109]. [score:1]
[1 to 20 of 7 sentences]
38
[+] score: 32
In the present study, miR-451 expression in the BP muscle of the grazing cattle was temporarily up-regulated at 2 mo compared to the housed cattle, which suggests the positive effect of grazing on miR-451 expression in skeletal muscles, as well as on miR-206 and miR-208b [16]. [score:7]
We recently reported that miR-206 and miR-208b expressions in the biceps femoris (BP) muscle of grazing Japanese Shorthorn cattle were elevated after 4 months of grazing; these miRNAs are associated with temporary down-regulation of MyoD and fast-type myosin heavy chain isoform [16], which could be associated with conversion of the bovine skeletal muscle type with miRNA profile [17]. [score:6]
Although miR-206 and miR-208b expression in the BP muscle of cattle was up-regulated by grazing [16], the unchanged muscle-specific miRNA levels in circulation in our study suggest that grazing is a mild form of exercise or movement for cattle that does not induce muscle damage. [score:6]
Although the effect of nutrition or movement during grazing could not be separately evaluated, the grazing of cattle in our previous study [16] resulted in significant up-regulation of miR-208b and down-regulation of miR-206, MyoD and MyHC-2x, which indicated that the skeletal muscle of the grazing cattle physiologically adapted to the increased movement. [score:5]
Recent studies of muscle-specific miRNAs such as miR-1, miR-133a/b, miR-206, and miR-208b have indicated their roles in the development or specification of skeletal muscle [5– 7]. [score:2]
MicroRNA-206 is overexpressed in the diaphragm but not the hindlimb muscle of mdx mouse. [score:2]
Serum levels of miR-1, miR-133a/b, and miR-206 are increased in patients of human Duchenne muscular dystrophy [18, 19] and of rhabdomyosarcoma tumor [20], and that the miR-21 level is affected in various types of cancers [21– 24]. [score:1]
Muscle-specific miRNAs such as miR-1, miR-133a, miR-206, miR-208b, and miR-499 were not significantly detected in the plasma exosomes across all samples (i. e., grazing and housed during experiment) except for miR-486 (0.18%) and a trace of miR-133b (< 0.001%). [score:1]
In the present study, among the 231 exosomal miRNAs detected in the cattle plasma, muscle-enriched miR-486 and a trace of miR133b were detected, but miR-1, miR-133a, miR-206, miR-208b, and miR-499 were not detected. [score:1]
Indeed, muscle-specific miR-1, miR-133a/b, miR-206, and/or miR-208b in circulation have been shown to be changed by muscle-damaging downhill walking [31] and marathon running in humans [39, 57]. [score:1]
[1 to 20 of 10 sentences]
39
[+] score: 29
miR-206 is up-regulated in ERα -negative breast tumors and cell lines and inhibits ERα translation by binding to the 3′UTR of ERα mRNA (47). [score:8]
These events may lead to the activition of other ER isoforms which induce the expression of some miRNAs, such as miR-206, miR-18a, miR-18b, miR-221 and miR-222, leading to further inhibition of ERα expression (49)and the activation of other pathways controlling cell growth and proliferation. [score:7]
The latter study also suggested that miR-206 expression was strongly inhibited by ERα agonists (E2 and PPT), but not by an ERβ agonist (DPN) and progesterone in MCF-7 cells. [score:5]
Similar to miR-206, miR-18a, miR-18b and miR-221/222 are also up-regulated in ERα -negative cell lines, suggesting an important role of these miRNAs in the development of ERα -negative breast cancers (48, 49). [score:5]
In addition to miR-206, ERα mRNA is also a direct target of miR-18a, miR-18b, miR-193b, miR-302c and miR-221/222 in breast cancer cells. [score:4]
[1 to 20 of 5 sentences]
40
[+] score: 29
Among miRNAs up-regulated during WJ-MSC neuronal differentiation, miR-34a and miR-206 were also up-regulated in neuronal precursors derived from BM-MSC [21] (Figures 1B, underlined). [score:7]
MiR-206 is one of the miRNAs down-regulated by IL-1α, while miR-34a is still abundant in day 12 neurons in the presence or absence of IL-1α [21]. [score:4]
MiR-34a and miR-206 were the only 2 miRNAs which were commonly down-regulated during neuronal differentiation in both WJ-MSC and BM-MSC. [score:4]
Another 11 miRNAs (miR-206, miR-34a, miR-374, miR-424, miR-100, miR-101, miR-323, miR-368, miR-137, miR-138 and miR-377) were abundantly expressed in transdifferentiated neuronal progenitors. [score:3]
In contrast, 11 miRNAs (hsa-miR-206, hsa-miR-34a, hsa-miR-374, hsa-miR-424, hsa-miR-100, hsa-miR-101, hsa-miR-323, hsa-miR-368, hsa-miR-137, hsa-miR-138 and hsa-miR-377) were abundantly expressed in day 9 neuronal progenitors (Figures 1B and 2A). [score:3]
In bone marrow MSCs, miR-130a and miR-206 have been show to regulate the synthesis of neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells [21]. [score:2]
In bone marrow MSCs, miR-130a and miR-206 have been show to regulate the synthesis of neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. [score:2]
It has been confirmed previously that miR-206 can regulate the synthesis of neurotransmitter substance P in human BM-MSC-derived neuronal cells [21]. [score:2]
Among these miRNAs, miR-34a and miR-206 were the only 2 miRNAs been linked to BM-MSC neurogenesis. [score:1]
It has been reported that in BM-MSC-derived neurons (day 12), 32 miRNAs are altered, including miR-206 and miR-34a [21]. [score:1]
[1 to 20 of 10 sentences]
41
[+] score: 29
We found that the expression of muscle miRNAs, including miR-1a, miR-133a and miR-206, was up-regulated in the skeletal muscle of mdx mice. [score:6]
Northern blot analyses further confirmed a significantly increased expression of miR-206, whereas the expression of miR-1 modestly increased in the muscle muscle of mdx mice (Figure 1B, C). [score:5]
This mutation creates a binding site for miR-1 and miR-206, leading to the translational repression of myostatin, which phenocopies the "muscle doubling" that results from the loss of myostatin in mice, cattle, and humans [29, 30]. [score:4]
We found that the expression miR-133a, together with that of miR-206 and miR-1a, was induced in the skeletal muscle of mdx mice. [score:3]
We found that the expression levels of miR-1, miR-133 and miR-206 were higher in the skeletal muscle of one month-old mdx mice (Figure 1A). [score:3]
A subset of miRNAs, miR-1, miR-133, miR-206 and miR-208, are either specifically or highly expressed in cardiac and skeletal muscle and are called myomiRs [6, 7, 13]. [score:3]
Furthermore, miR-1 and miR-206 also participate the regulation of skeletal muscle satellite cell proliferation and differentiation [8]. [score:2]
Among them, miR-1, miR-133, miR-206, miR-208 and miR-499 have been described as muscle specific miRNAs, or myomiRs [6, 13]. [score:1]
For example, miR-206 levels are elevated in the diaphragm muscle of the mdx mouse, an animal mo del of muscular dystrophy [27]. [score:1]
Briefly, 20 μg of total RNAs isolated from skeletal muscle of 1 month old mdx and the control mice (Figure 1), or from the heart, skeletal muscle and liver tissues of miR-133a-1 transgenic and the control mice (Figure 2), were used and miRNA oligonucleotides with corresponding miRNAs (miR-1a, miR-133a and miR-206) sequences were used as probes. [score:1]
[1 to 20 of 10 sentences]
42
[+] score: 28
Several groups have used microarray data to examine the expression changes when a single miRNA changes, and we used the mean absolute expression approach described recently by Arora and Simpson [49] and also the tissue-centric approach described by Sood et al. [50] to determine whether we could detect shifts in the average expression of mRNA targets of the muscle-specific miRNAs (miR-1, miR-133a/b and miR-206, collectively known as 'myomirs') in human skeletal muscle. [score:9]
CDC42 and PTBP1 were selected for study because they ranked highly as targets of miR-133/miR-206 in the TargetScan database and both proteins are relevant for muscle cell differentiation and metabolism [57, 58]. [score:5]
Over -expression of miR-1 [55] or miR-206 [86] in mouse myoblasts accelerates differentiation into myotubes whereas over -expression of miR-133 promotes proliferation [55]. [score:5]
ANOVA indicated that miR-133a (F = 11.8, P < 0.0001) was significantly different between the three groups, miR-206 expression more modestly altered (F = 4.5, P = 0.02) and miR-1 and miR-133b were unchanged (Figure 2c). [score:3]
Interestingly, reduction in miR-133a using an antagomir (Figure S4A in Additional file 1) had an indirect effect on the other myomirs, such that miR-133b (expected due to sequence similarity) and miR-206 (unexpected) were substantially reduced. [score:2]
miR-133a (P < 0.001) and miR-206 (P = 0.04) were significantly reduced in T2D patients when compared with expression levels in healthy controls. [score:2]
Subsequently, we checked miR-206, which associated more modestly with these clinical parameters, and miR-1, which did not associate with any of these clinical parameters. [score:1]
Most studied are miR-133, miR-206 and miR-1, which are all induced during differentiation of myoblasts into myotubes [28]. [score:1]
[1 to 20 of 8 sentences]
43
[+] score: 25
Regeneration-miRNAs were up-regulated (miR-31, miR-34c, miR-206, miR-335, miR-449, and miR-494), while degenerative-miRNAs (miR-1, miR-29c, and miR-135a) were down-regulated in mdx mice and in DMD patients’ muscles. [score:7]
In contrast with the other myomiRs, miR-206 shows an increased expression in distrophic mdx muscle because it activates satellite cell differentiation program through Pax7 and HDAC4 repression. [score:3]
An up-to-date list of the identified targets of miR-1, miR-133 and miR-206, together with a plethora of specific muscular pathways they are involved in, is reported in a recent review [40] and some of these will be also discussed in the next paragraph to highlight how these important families of miRNAs contribute to determine typical deficiencies occurring in a pathological muscular context. [score:3]
Another interesting target of miR-206 is Utrophin (Utrn), a dystrophin protein homolog, involved in a compensatory mechanism in DMD pathology [31, 66, 74]. [score:3]
Gambar della and co-workers profiled a specific pattern of myomiRs involved in myogenesis of cardiac and skeletal muscle and found lines of evidence of miR-206 overexpression in five DM1 patients [69]. [score:3]
Also miR-31, as miR-206, has a preferential localization in regenerating myoblasts, and is highly expressed in Duchenne muscles, probably due to an intensified activation of satellite cells. [score:3]
Relying on ability of myomiRs to orchestrate muscular proliferation and differentiation, the genomic region of miR-206/-133b has been analyzed in detail. [score:1]
It is possible to functionally define miR-133 as enhancer of myoblast proliferation while miR-1 and miR-206 as enhancers of skeletal muscle differentiation [37– 40]. [score:1]
miR-1, miR-133a/b and miR-206 are largely studied and defined muscle-specific miRNAs (myomiRs). [score:1]
[1 to 20 of 9 sentences]
44
[+] score: 24
Other miRNAs from this paper: hsa-mir-184
In this study, we used qPCR to examine differential miRNA expression and discovered that miR-184 and miR-206 were significantly up-regulated in CCDC19 -overexpressing A549 and SPCA1 lung cancer cells compared to their respective controls. [score:7]
In a previous report, miR-206, but not miR-184, was been found to act as a tumour suppressor to inhibit cell growth, invasion and metastasis in lung cancer [35]. [score:5]
Expression of miR-184 and miR-206 was markedly induced in CCDC19 -overexpressing A549 cells (Fig. 5A). [score:5]
We observed an inverse change in miR-184 and miR-206 after knocking down ectopic CCDC19 expression in A549 and SPCA1 NSCLC cells (Fig. 5C and D). [score:4]
CCDC19 positively modulates the expression of miR-184 and miR-206. [score:3]
[1 to 20 of 5 sentences]
45
[+] score: 24
In the pre-miR-206 downregulated genes, the regression mo del showed that miR-1 and miRNA-206 have the highest coefficient that explains 25% of the downregulated genes. [score:7]
88 genes were identified to be down regulated after pre-miR-1 treatment, 83 were downregulated after pre-miR-206 treatment, and 51 were down regulated after pre-miR-27b treatment. [score:6]
For example, in [26] LNCaP cell lines were treated with pre-miRNA (pre-miR-1, pre-miR206, and pre-miR27b) and downregulated genes were identified using differential gene expression analysis. [score:6]
To demonstrate the applicability and effectiveness of using Lasso regression mo deling to identify miRNAs whose targets are enriched in gene lists, we used affymetrix gene expression data from LNCaP cell lines treated with pre-miR-1, pre-miR-27b and pre-miR-206 that was retrieved from [26] under the access number GSE31620. [score:5]
[1 to 20 of 4 sentences]
46
[+] score: 24
Other miRNAs from this paper: hsa-mir-199b, hsa-mir-449a, hsa-mir-433
Although it is known that miRNAs possess the ability to regulate gene expression by decreased translation or enhanced degradation of the target message, some studies demonstrated that Notch3 might be downregulated at both the protein and mRNA levels by miR-206 in mouse and humans. [score:11]
It seems, therefore, that the tumour suppressive capacity of miR-206 can be explained by both direct Notch3 signaling inhibition and indirect cross-talk with other signaling pathways involving CDH2 and MMP-9 [78]. [score:7]
The suppression of the Notch3 protein by miR-206 is probably possible by direct miR-206 binding to the 3’-UTR of Notch3. [score:4]
This suggests that miR-206 regulation is not restricted to the post-transcriptional level, but may also be detected at the transcriptional level [77]. [score:2]
[1 to 20 of 4 sentences]
47
[+] score: 24
Other miRNAs from this paper: mmu-mir-206
FTY720 Increases BDNF in Old A53T Tg in Association with miR206-3p Down-regulation. [score:4]
Using this mo del allowed us to show for the first time that 1) long term FTY720 can be well tolerated and significantly improve gut function (Figs. 2 and 3); 2) FTY720 significantly reduces gut aSyn pathology even when given after the onset of synucleinopathy (Figs. 4 and 6); 3) FTY720 stimulates early and sustained up-regulation of BDNF (Figs. 5 and 6), which in young mice increased both pro-BDNF and mature BDNF and in old mice increased mature BDNF in association with reduced miR206-3p (Fig. 5); 4) blockade of Trk-B receptors in young A53T Tg mice significantly increased aSyn levels and aSyn aggregation in the gut; and 5) there is a huge loss of total TH immunoreactivity in neurons of the PNS containing aggregated aSyn (Figs. 1 and 4), similar to our prior findings in CNS dopaminergic neurons (42). [score:4]
Data represent means ± S. E., except for miR206-3p and BDNF whisker box plots generated using REST 2009 software, which demonstrate the median (white dashed line in boxes), interquartile ranges 1 and 3 (top and bottom edges of boxes), and maximum and minimum expression values (top and bottom whiskers). [score:3]
BDNF mRNA and miR206-3p expression were calculated using the comparative Ct method (2 [−ΔΔ] [Ct]) and relative expression software tool (REST) that is available online (87). [score:3]
B, the expression of the regulatory microRNA, miR206–3p, was significantly lower in response to FTY720 treatment of aged Tg mice as compared with vehicle Tg mice. [score:3]
Finally, miRNAs are thought to play a role in age -associated neurodegeneration (75), and we saw changes in miR206-3p only in aged A53T Tg mice. [score:1]
FIGURE 5. FTY720 stimulates long term increases in BDNF protein in aging Tg mice in association with significantly lower levels of miR206–3p. [score:1]
Levels of BDNF mRNA were similarly increased above vehicle levels for mice given ANA-12, FTY720 + ANA-12, or FTY720 (∼2.4–2.5-fold) (Fig. 6 D), which is quite different from our findings in old A53T mice that showed no change in BDNF mRNA yet had significantly more mature BDNF and a decrease in miRNA206-3p, which was associated with a parallel increase in BDNF protein. [score:1]
As an additional control, we measured miR206-3p expression in MN9D dopaminergic neuronal cells after treating them with FTY720, which we previously found increases BDNF levels in these cells (26). [score:1]
The young A53T mice in our ANA-12 studies showed no changes in miR206-3p in any treatment condition (not shown). [score:1]
The decrease in miR206–3p was further validated in a control experiment with dopaminergic MN9D cells treated with 160 n m FTY720 for 24 h. (n = 8 mice/treatment group); *, p < 0.05; ***, p < 0.001. [score:1]
Similarly to Tg gut, MN9D cells also significantly decreased miR206-3p in response to FTY720 treatment (Fig. 5 B, red box plot, p = 0.034), suggesting a mechanism whereby FTY720 may have improved gut motility by increasing BDNF levels. [score:1]
[1 to 20 of 12 sentences]
48
[+] score: 24
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-96, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, hsa-mir-196a-1, hsa-mir-198, hsa-mir-129-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-196a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-204, hsa-mir-210, hsa-mir-211, hsa-mir-212, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-216a, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-140, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-184, hsa-mir-185, hsa-mir-195, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-365a, hsa-mir-365b, hsa-mir-375, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-382, hsa-mir-383, hsa-mir-151a, hsa-mir-148b, hsa-mir-338, hsa-mir-133b, hsa-mir-325, hsa-mir-196b, hsa-mir-424, hsa-mir-20b, hsa-mir-429, hsa-mir-451a, hsa-mir-409, hsa-mir-412, hsa-mir-376b, hsa-mir-483, hsa-mir-146b, hsa-mir-202, hsa-mir-181d, hsa-mir-499a, hsa-mir-376a-2, hsa-mir-92b, hsa-mir-33b, hsa-mir-151b, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-301b, hsa-mir-216b, hsa-mir-103b-1, hsa-mir-103b-2, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-219b, hsa-mir-203b, hsa-mir-451b, hsa-mir-499b, hsa-mir-378j
niloticus), miR-206 targets IGF-1 and inhibits its action (Yan, Zhu, et al. 2013), indicating the importance of miRNAs in hypothalamic–pituitary pathway. [score:5]
Estrogens regulate transcription of some miRNAs, such as miR-21 and miR-221; in contrast, other miRNAs such as let-7, miR-22, miR-196b, or miR-206 target estrogen receptor alpha transcript (Cochrane et al. 2011). [score:4]
In another study, four miRNAs (miR-1, miR-27a, miR-133a, and miR-206) were differentially expressed during skeletal muscle development of Nile tilapia (Yan et al. 2012a). [score:4]
Similarly, by comparing skeletal muscle of different stages (larvae, 1-, and 2-year old) of common carp (Cyprinus carpio), Yan et al. (2012) reported an increase in miR-1, miR-21, miR-133a-3p, and miR-206 expression with age. [score:3]
In their mo del, MRFs activate miR-1/miR-206 in the committed myoblasts, and these miRNAs target residual pax3 during the progenitor-to-myoblast transition, and they control transitional timing by repressing pax3. [score:3]
For example, miR-206 is expressed both maternally and zygotically in zebrafish, and it is essential in controlling cell movements during the gastrulation (Liu et al. 2012). [score:3]
However, other miRNAs such as miR-34, miR-200a, miR-200b, and miR-206 are also found abundantly during the embryogenesis. [score:1]
For instance, a single-nucleotide polymorphism (SNP) at the 3′-UTR of mystotin gene in Texel sheep allows binding by miR-1 and miR-206, which in effect creates muscular hypertrophy (Clop et al. 2006). [score:1]
[1 to 20 of 8 sentences]
49
[+] score: 23
One study suggested that the rapid removal of SNAI1 and SNAI2 at the onset of differentiation is mediated by miR-30a and miR-206, respectively, resulting in the upregulation of myogenin and a dependent increase in the miR-30a and miR-206 expression [31]. [score:6]
Dai et al. [27] confirmed the mechanism in which miR-1 and miR-206 positively regulate bovine skeletal muscle satellite cell myogenic differentiation via the downregulation of PAX7 and HDAC4. [score:5]
Moreover, miR-206 directly targets cyclin D1 (CCND1) and DNA polymerase α (POLA1), reducing the proliferation rate of myogenic cells [30]. [score:4]
MiR-1 and miR-206 were also found to inhibit PAX3 [28] and NOTCH3 [29] allowing differentiation to proceed. [score:3]
A few high-throughput studies have confirmed some of the identified miRNAs (miR-1, miR-128, miR-133a, miR-133b, miR-206, miR-222, and miR-503) as common for skeletal muscle development in mouse, human, pig, common carp [11], and cattle [25]. [score:2]
Cell culture experiments have shown that miR-1 and miR-206 promote muscle cell differentiation, whereas miR-133 enhances cell proliferation. [score:1]
It is plausible that in HER/LIM cells, the differentiation progression is accelerated via similar mechanisms involving miR-1, miR-133, miR-206, and myogenin, resulting possibly in enhanced myotube formation observed in the primary cultures of the skeletal muscle with a HER/LIM origin (Fig. 1). [score:1]
Moreover, some of identified molecules were also annotated as taking part in myoblast proliferation (miR-1, -128, -133a, -133b, -139, and -206); myocyte function (miR-31, -133a, -145, and -222); myoblast fusion (miR-206, -222, and -486); and satellite cell activation (miR-1 and -206) (Fig.   3). [score:1]
[1 to 20 of 8 sentences]
50
[+] score: 23
Moreover, the myogenic miRNA miR-206 also showed a higher expression level in LR and distinctly different distinct expression patterns between breeds from 49 to 77 dpc. [score:5]
Koutsoulidou A Mastroyiannopoulos NP Furling D Uney JB Phylactou LA Expression of miR-1, miR-133a, miR-133b and miR-206 increases during development of human skeletal muscleBMC Dev. [score:4]
Thus, miR-206 plays an opposite role to miR-186 and showed higher expression in LR than in LT across the studied embryonic stages (G1 up). [score:3]
miR-206 promotes the differentiation of skeletal muscle cells through the inhibition of histone deacetylase 4(HDAC4) which controls muscle differentiation [18]. [score:3]
Among the 35 miRNAs found in the network, miR-133b and miR-206 are known muscle-specific miRNAs that are induced during muscle differentiation and increase the expression of myogenic determination and differentiation factors (such as MEF2A and MEF2C in our network) 24, 25. [score:3]
Though miR-206 was not selected as a DE miRNAs, as it failed to meet the selection criteria, this miRNA indeed showed distinct expression patterns between breeds. [score:3]
Some of miRNAs showed multiple strong interactions with other genes; some of these interactions included well-known, crucial myogenic miRNAs and genes (miR-206, miR-133b, miR135-5p, MEF2A, MEF2C, etc. ) [score:1]
Kim HK Lee YS Sivaprasad U Malhotra A Dutta A Muscle-specific microRNA miR-206 promotes muscle differentiationJ. [score:1]
[1 to 20 of 8 sentences]
51
[+] score: 23
Based on the fold changes, qRT-PCR was performed to validate microarray results on 12 miRNAs, specifically miRNAs up-regulated in both heart and plasma (miR-660-3p, miR-665, miR-1285-3p and miR-4491), down-regulated in heart but up-regulated in plasma (miR-206 and miR-1268b), up-regulated in heart but down-regulated in plasma (miR-130-3p, miR-199a and miR-330-3p), down-regulated in both heart and plasma (miR-221-30, miR-487b-3p and miR-4288), were chosen for validation test in the plasma of 45 control and 45 CHF patients. [score:19]
Interestingly, among these miRNAs, miR-206 was also reported to play important roles via inhibition of TIMP3 in cardiac fibroblasts in heart failure mo dels [19]. [score:3]
As a result, 8 of the 12 selected miRNAs (miR-660-3p, miR-665, miR-1285-3p, miR-4491, miR-206, miR-1268b, miR-130-3p and miR-330-3p) were successfully validated in the second cohort. [score:1]
[1 to 20 of 3 sentences]
52
[+] score: 23
miR-206 inhibition should theoretically inhibit skeletal muscle differentiation and prevent subsequent fusion. [score:5]
This combination of cytokines and small molecules with miR-206 inhibition blocked terminal skeletal muscle differentiation while simultaneously promoting CM differentiation. [score:3]
However, they did not interfere with muscle differentiation if they were added sequentially after initial IWR-1 and miR-206 inhibitor treatment (Supplementary Fig. 1a). [score:3]
In the 4 factor artificial muscle tissue protocol (4F-AMT, Figure 2c), AMT was constructed as described, cultured in DM, and treated with 4 chemical factors: miR-206 inhibitor (100 pmol, Life Technologies), IWR-1 (10 uM), LiCl (10 mM), and BMP-4 (25 ng/ml) at different time points as illustrated in Figure 2c. [score:3]
For transfection of miR-206 inhibitor, X-treme Gene siRNA transfection reagent (Roche) was used according to the manufacturer's instructions. [score:3]
In our initial studies, we tested 4 chemical factors (miR-206 inhibitor, IWR-1, LiCl, and BMP-4) individually and in combination for their ability to reduce skeletal myotube formation and stimulate connexin-43 (GJA1) gap junction formation. [score:3]
Taken together, these data suggest that timed cytokine/small molecule treatment and transient miR-206 inhibition were sufficient to produce the desired phenotype. [score:3]
[1 to 20 of 7 sentences]
53
[+] score: 21
Other miRNAs from this paper: hsa-mir-133a-1, hsa-mir-133a-2
Indeed, we demonstrated that DNMT3B depletion was able to significantly up-regulate the expression of miR-133a and miR-206, two well-established myomiRs essential in promoting muscle cell differentiation (Figure 5E). [score:6]
Compared to mocked control cells, si-DNMT3B samples showed of a marked expression of MYOD1, followed by Myogenin and myomiR (miR-133a and miR-206) up-regulation. [score:5]
MYOD1 is a master regulator of myogenesis, since it normally triggers the down-stream molecular events that switch myoblasts from a growing phase to a differentiated state, by directly promoting the expression of miR-206 and many other genes involved in myogenesis [45, 46]. [score:5]
D. Expression of myogenic miRNAs, miR-133a and miR-206, by Q-PCR experiments in RD cells transfected with DNMT3B or NC siRNAs for 72 h. Expression of each miRNA was normalized to U6 levels and plotted as fold change relative to si-NC samples. [score:5]
[1 to 20 of 4 sentences]
54
[+] score: 21
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-140, hsa-mir-125b-2, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-155, hsa-mir-181b-2, hsa-mir-106b, hsa-mir-302a, hsa-mir-34b, hsa-mir-34c, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, gga-let-7i, gga-let-7a-3, gga-let-7b, gga-let-7c, gga-mir-125b-2, gga-mir-155, gga-mir-222a, gga-mir-221, gga-mir-92-1, gga-mir-19b, gga-mir-20a, gga-mir-19a, gga-mir-18a, gga-mir-17, gga-mir-16-1, gga-mir-15a, gga-mir-1a-2, gga-mir-206, gga-mir-223, gga-mir-106, gga-mir-302a, gga-mir-181a-1, gga-mir-181b-1, gga-mir-16-2, gga-mir-15b, gga-mir-140, gga-let-7g, gga-let-7d, gga-let-7f, gga-let-7a-1, gga-mir-146a, gga-mir-181b-2, gga-mir-181a-2, gga-mir-1a-1, gga-mir-1b, gga-let-7a-2, gga-mir-34b, gga-mir-34c, gga-let-7j, gga-let-7k, gga-mir-23b, gga-mir-27b, gga-mir-24, gga-mir-122-1, gga-mir-122-2, hsa-mir-429, hsa-mir-449a, hsa-mir-146b, hsa-mir-507, hsa-mir-455, hsa-mir-92b, hsa-mir-449b, gga-mir-146b, gga-mir-302b, gga-mir-302c, gga-mir-302d, gga-mir-455, gga-mir-367, gga-mir-429, gga-mir-449a, hsa-mir-449c, gga-mir-21, gga-mir-1458, gga-mir-1576, gga-mir-1612, gga-mir-1636, gga-mir-449c, gga-mir-1711, gga-mir-1729, gga-mir-1798, gga-mir-122b, gga-mir-1811, gga-mir-146c, gga-mir-15c, gga-mir-449b, gga-mir-222b, gga-mir-92-2, gga-mir-125b-1, gga-mir-449d, gga-let-7l-1, gga-let-7l-2, gga-mir-122b-1, gga-mir-122b-2
When tissues were compared under the non-infected state, all differentially expressed miRNAs were expressed at higher levels in lungs than tracheae with the only exception of miR-206, which showed a higher expression level in non-infected trachea than lung (Table 6). [score:6]
We can conclude that miR-206 has an opposite regulatory role in lungs and tracheae or might have different targets in different tissues and therefore play different roles in host-virus interactions. [score:4]
More interestingly, miR-206 was up-regulated in virus infected vs. [score:4]
Target genes for miR-206 were associated with monocyte macrophage differentiation, suggesting they maybe associated with antigen presentation. [score:3]
In the tissue comparison under the non-infected state, miR-206 was the only miRNA that had higher expression level in tracheae than in lungs. [score:3]
We hypothesize that miR-34b, miR-34c, miR-206, miR-1458 and miR-1612 might be some of the most important miRNAs associated with AIV infection. [score:1]
[1 to 20 of 6 sentences]
55
[+] score: 21
Up-regulation of miR-206 can slow down the progression of ALS and promote regeneration of neuromuscular synapses, but this up-regulation was also identified in other diseases, such as schizophrenia (Hansen et al., 2007) and cerebral ischemia (Jeyaseelan et al., 2008), suggesting that up-regulation of miR-206 is not specific for ALS. [score:12]
The miR-29a-special antagomir, demonstrated increased lifespan in male SOD1 [G93A] mice by reducing ER stress (Nolan et al., 2014); Inhibition of miR-23a ameliorates skeletal muscle mitochondrial function in ALS by increasing the PGC-1α signaling, which was involved in mitochondrial biogenesis and function (Russell et al., 2012); the anti-miR-155 significantly extends survival and disease duration in the SOD1 [G93A] mouse mo del (Koval et al., 2013), and the miR-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice partly through fibroblast growth factor and histone deactylase 4 signaling pathways (Williams et al., 2009). [score:5]
However, as a biomarker, miR-206 was reproduced by only one study, which reported that miR-206 was up regulated in serum from SOD1 ALS mice and ALS patients (Toivonen et al., 2014). [score:2]
MiRNAs, as a key regulator, was first reported by Williams et al. That study showed that miR-206 slowed ALS progression and promoted regeneration of neuromuscular synapses in mice mo del (Williams et al., 2009). [score:2]
[1 to 20 of 4 sentences]
56
[+] score: 20
Coda et al. showed that G6PD is strongly downregulated in RMS cells upon miR-206 -induced differentiation, confirming that G6PD is a direct target of miR-206 [42]. [score:7]
Based on the TargetScan, miRanda, and Diana microT computational algorithms, we determined that miR-1, miR-133a, and miR-206 might target a combined site in the G6PD 3′-UTR gene sequence. [score:5]
However, neither miR-133a nor miR-206 expression differed in HR-HPV+ cervical cancer cells compared to control cells (Figure 4A). [score:2]
By contrast, G6PD mRNA was not enriched in miRNPs following transfection with either miR-133a or miR-206 (Figure 2A–2B and Figure 2A–2C). [score:1]
Among the many miRNAs identified, miR-1, miR-133a, and miR-206, each of which were predicted by all three software programs, were chosen for further validation. [score:1]
Figure 2RIP-Chip revealed that G6PD mRNA was recruited to the miRNPs to the greatest degree following transfection with miR-1. (A-a) Enrichment in AGO-miRNPs after miR-1 transfection, n = 3161; (A-b) Enrichment in AGO-miRNPs after miR-133a transfection, n = 3336; (A-c) Enrichment in AGO-miRNPs after miR-206 transfection, n = 5958. [score:1]
Co-immunoprecipitation (co-IP) revealed that transfected miR-1, miR-133a, and miR-206 were specifically incorporated into miRNPs in both Hela (Figure 1A) and Siha cells (Figure 1B). [score:1]
After 24 hours, cells were transfected with 25 nM “Pre-miRNA” (Ambion) for has-miR-1, has-miR-133a, has-miR-206, or Negative Control (NC, Ambion, Austin, TX, sense sequence AGUACUGCUUACGAUACGG) using RNAiMAX (Invitrogen, Carlsbad, CA) according to the manufacturer's instructions [13]. [score:1]
RIP-Chip revealed that G6PD mRNA was recruited to the miRNPs to the greatest degree following transfection with miR-1. (A-a) Enrichment in AGO-miRNPs after miR-1 transfection, n = 3161; (A-b) Enrichment in AGO-miRNPs after miR-133a transfection, n = 3336; (A-c) Enrichment in AGO-miRNPs after miR-206 transfection, n = 5958. [score:1]
[1 to 20 of 9 sentences]
57
[+] score: 20
We were interested in identifying predicted co-repression of target transcripts by all three mature miRNAs observed in C2C12s (mir24-2, mir-351, and mir-26a-2), reasoning that they might act in concert to exert effects on transcripts comparable to much more highly expressed miRNAs that are solitary actors such as mir-206. [score:5]
Heatmap showing correct expression of control miRNA probe sets for muscle (mir-133a and mir-206) and ES cell control (mir-293 containing cluster). [score:3]
While superficially it seems that the mir-24 containing cluster is a generalized differentiation controlling locus, mir-24 has been observed to be specifically expressed in porcine satellite cells in a reciprocal fashion to mir-206 [25]. [score:3]
In mammals, mir-206 can be activated by MyoD expression [17] and remains active in terminally differentiated muscle fibers [18], yet is repressed in developing somites of chicken embryos in response to FGF4 signalling [19]. [score:3]
Completely malformed musculature results when mir-1 is absent during Drosophila larvae development [23], and interference with mir-206 in mouse maintains C2C12 cells in a cycling state [24], implying that it is a key requirement for differentiation to proceed. [score:2]
In agreement to this, mir-206 is nearly absent in proliferating porcine satellite cells but is greatly induced during murine C2C12 differentiation [25], [26], suggesting that miRNAs participate in muscle development. [score:2]
Increases in abundance of three major muscle-specific miRNAs (mir-1, mir-133, and mir-206) have been observed during muscle cell differentiation in the mouse, Drosophila, and the zebrafish [15], [16]. [score:1]
After data normalization and analysis, 148 probe sets with >2 fold enrichment in muscle RNA versus ES derived RNA were identified, including muscle control probe sets designed against known muscle miRNAs mir-206, mir-133a/b (Figure S6), as well as the let-7 family miRNAs. [score:1]
[1 to 20 of 8 sentences]
58
[+] score: 20
Having demonstrated that miR-1 is able to target PAX7, as already reported for miR-206 [65], which is consistently upregulated in YY1 over -expressing myoblasts, the authors depicted an anti-myogenic network in which YY1 plays a central role in repressing miR-1/miR-206 (Figure 4). [score:8]
Although no direct epigenetic regulation of the expression of miR-1 and miR-206 clusters has been highlighted in RMS, a recent study provided several evidences linking these miRNAs to the epigenetic machinery in normal myoblasts [63]. [score:5]
In this work, YY1 was shown to regulate the expression of miR-1 and miR-206 clusters in murine myoblasts in vitro and in vivo. [score:4]
” To this group belong three miRNA clusters, miR-1-1/miR-133a-2, miR-1-2/miR133a-1 and miR-206/miR-133b, encoded by three bicistronic miRNA genes on separate chromosomes (reviewed in [62]). [score:1]
Moreover, they discovered a previously unknown enhancer upstream of miR-206 and miR-133b coding regions (E4) showing YY1 binding site. [score:1]
Additional links with epigenetic networks in myoblasts have been shown for both miR-1 and miR-206 clusters. [score:1]
[1 to 20 of 6 sentences]
59
[+] score: 19
they are “Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease” [6], “microRNA-133: expression, function and therapeutic potential in muscle diseases and cancer” [7] and “microRNA-1/133a and microRNA-206/133b clusters:Dysregulation and functional roles in human cancers” [5], respectively. [score:9]
Although these miRs have the same specificity of tissue expression, mature miRNA sequence present variant nucleotiedes (Figure 1A shows the representative gene structure of miR-133b/miR-206 clusters and each mature miRNA sequence), this also explains to a certain extent its function may be different. [score:3]
In addition, another original intention for this review is that there has been individual review for each myomiRs but miR-133b, these independent reviews about miR-133 [7]/a [10], miR-1 [11– 13], miR-206 [14, 15] and miR-133b which we review in here is so particularly important for us to understand the jointly or independently role of myomiRs acting in human disease. [score:3]
MicroRNA families miR-1 and miR-133, and single miR-206 are collectively known as the muscle-specific miRNAs (“myomiRs”) because of they are highly conserved in the musculatures across species [8]. [score:1]
miR-133b and miR-206, two isomers of miR-1 and miR-133a form different clusters located in on chromosomes 6p12.2, 20q13.33 and 18q11.2, respectively. [score:1]
Also in lung cancer, the experiment in vivo showed alteration of serum miR-206 and miR-133b may have to do with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [91]. [score:1]
Figure 1(A) The representative gene structure of miR-133b/miR-206 clusters and the mature miRNA sequence of these two miRNAs; miR-133b/miR-206 clusters located in on chromosomes 6p12.2 and miR-133b gene transcript is located within the precursor of the long non-coding RNA linc-MD1. [score:1]
[1 to 20 of 7 sentences]
60
[+] score: 19
Furthermore, miR-206 is highly expressed in newly regenerated fibres (63), is upregulated in skeletal muscle 7 days after cardiotoxin injury, and miR-206 knockout mice exhibit delayed muscle regeneration (64). [score:7]
miR-206 expression was increased in mdx TA muscle relative to wild-type animals, as described previously (21) but expression was not altered after exercise. [score:5]
Notably, miR-1, miR-133 and miR-206 are among the most abundant miRNA species in myocytes (compromising more than 25% of all miRNAs) (26) and are involved in the control of muscle homeostasis by coordinating both myoblast proliferation and differentiation (27, 28). [score:1]
Interestingly, it has been shown that administration of exogenous miR-1, miR-133, and miR-206 oligonucleotides in rats accelerates muscle regeneration (62). [score:1]
Notably, cellular miRNA and secreted ex-miRNA levels were positively correlated for all myomiRs (Pearson coefficients: 0.7809 (miR-1), 0.7515 (miR-133a), 0.8219 (miR-206); all P <  0.01,, Table S7). [score:1]
Most importantly, miR-1, miR-133a and miR-206 dynamics followed a similar pattern in both mouse strains (P-value of interaction factor P > 0.05 for all myomiRs, i. e. not significant). [score:1]
Despite slightly differing patterns of release, after 9 days the absolute levels of myomiRs in the media were similar for miR-206 (0.4 million copies/ml) and miR-133a (0.2 million copies/ml) and somewhat lower for miR-1 (0.04 million copies/ml). [score:1]
As with the primary human myoblasts, cellular and secreted levels of myomiRs in C2C12 cells were likewise strongly correlated (Pearson coefficients: 0.9291 (miR-1), 0.8878 (miR-133a), 0.8937 (miR-206); all P <  0.0001,, Table S7) whereas the non-myomiR controls were not correlated (miR-31 and let7-a) or had weak correlation coefficients (miR-16). [score:1]
Likewise, miR-133a levels increased progressively following exercise and miR-206 exhibited a very similar pattern but failed to reach statistical significance at the P <  0.05 level due to high inter-replicate variation. [score:1]
[1 to 20 of 9 sentences]
61
[+] score: 18
In the present study, we systematically determined the expression levels of plasma miRNAs in CAD patients, and our data firstly identified two plasma miRNAs (miR-206 and miR-574-5p) which significantly up-regulated in CAD patients compared with control subjects. [score:5]
The expression of these two miRNAs (miR-206 and miR-574-5p) remained significantly up-regulated in the CAD patients compared with the healthy controls (Figures 3A and 3B). [score:5]
Various studies indicate that besides the skeletal muscle-specific character, miR-206 may also play a pivotal role in cardiovascular diseases. [score:3]
The first study linking miR-206 to the heart was conducted by Shan et al. [31]. [score:1]
We obtained the following AUC values: miR-206, 0.607 (95% CI, 0.508–0.706) and miR-574-5p, 0.696 (95% CI, 0.609–0.787) respectively (Figures 4A and 4B). [score:1]
The gene for human miR-206 (hsa-miR-206) is localized on chromosome 6 in a bicistronic cluster together with the gene for miR-133b, the later refers to a skeletal muscle-specific myomiR [29, 30]. [score:1]
The authors showed that in a mouse mo del of myocardial infarction, levels of miR-1 and miR-206 are increased in infarcted tissue. [score:1]
Limana et al. [32] demonstrated that an increase in miR-206 was also observed in a rat mo del of heart failure and was even more prominent in mice treated with high mobility group box-1 protein (HMGB1). [score:1]
[1 to 20 of 8 sentences]
62
[+] score: 18
Eleven microRNAs were differentially expressed between the regenerating tail tip and base during maximum outgrowth (25 days post autotomy), including miR-133a, miR-133b, and miR-206, which have been reported to regulate regeneration and stem cell proliferation in other mo del systems. [score:4]
In mice, miR-1 and miR-206 regulate satellite cell proliferation via repression of Pax7 translation, thereby promoting myotube formation [48, 50]. [score:4]
Nine of these microRNAs have elevated expression in the tail base, including miR-1, miR-133a, miR-133b, and miR-206, which have been shown to play key roles in regulating skeletal muscle differentiation and function [37, 44– 48]. [score:4]
As shown in Fig.   3 miR-1a, miR-1b, miR-133a and miR-206 show increased expression in the proximal portion of the regenerating tail, while miR-184 and miR-2188 display an opposite pattern. [score:3]
During newt lens regeneration, miR-1 and miR-206 regulate cell proliferation [19]. [score:2]
Koning M Werker PMN van der Schaft DWJ Bank RA Harmsen MC MicroRNA-1 and microRNA-206 improve differentiation potential of human satellite cells: a novel approach for tissue engineering of skeletal muscle. [score:1]
[1 to 20 of 6 sentences]
63
[+] score: 17
Indeed, our reporter assays showed that miR-34a (Fig. S5 B and F), miR- 206 (Fig. S5 C and G), and miR-26a (Fig. S5 D and H) mimics suppressed the reporter activity of the constructs containing each target on the p72 3′UTR, whereas miR-206 mimic also decreased that of the construct containing a target on the p68 3′UTR (Fig. S5 A and E). [score:6]
Further analysis by TargetScan also revealed the existence of possible target sites of miR-206 and miR-34a/miR-206/miR-26a in the 3′UTRof p68 and p72, respectively, in a wide range of animal species. [score:5]
A-D) Schematic depiction of pGL3-Promoter plasmids fused to two tandem repeats of 3′UTR fragments containing a potential target site for miR-206 of p68 (A), miR-34a of p72 (B), miR-206 of p72 (C), or miR-26a of p72 (D) and corresponding mutants. [score:3]
For luciferase reporter assay, the 3′UTR fragments of the mouse p68 and p72 containing possible target sites for miR-145, miR-26a, miR-34a or miR-206 were amplified from genomic DNA of a C57BL/6 mouse by PCR using specific primers containing an XhoI site at the 5′end. [score:1]
miRNA mimics of miR-143, miR-145, miR-34a and miR-26a were purchased from Qiagen GmbH (Hilden, Germany), and miR-206 mimic was obtained from Ambion. [score:1]
This was intriguing, since miR-206 and miR-26a are a set of miRNAs whose processing was proven to depend on the p53/p68/p72 complex [14]. [score:1]
[1 to 20 of 6 sentences]
64
[+] score: 17
TWF1 has been detected as a target for microRNA-206 (miR-206) which is referred to microRNAs, fundamental post-transcriptional regulators inhibiting gene expression. [score:8]
Blocking TWF1 by miR-206 in human xenograft mo dels of breast cancer can suppress tumor invasion and metastasis by inhibiting the actin cytoskeleton dynamics [180]. [score:5]
Samaeekia R. Adorno-Cruz V. Bockhorn J. Chang Y. F. Huang S. Prat A. Ha N. Kibria G. Huo D. Zheng H. MicroRNA-206 inhibits stemness and metastasis of breast cancer by targeting MKL1/IL11 pathway Clin. [score:4]
[1 to 20 of 3 sentences]
65
[+] score: 16
Other miRNAs from this paper: hsa-mir-27a, hsa-mir-32, hsa-mir-198
In myoblasts, the downregulation of Fstl1 mRNA is regulated by muscle-specific miR-206 [32]. [score:5]
A list of predicted miRNA -binding sites in the 3′UTR of human FSTL1 with associated clinical relevance is provided in Supplemental Table 1. Table 1 MicroRNA -binding sites in FSTL1 gene Human microRNA Binding position in 3′UTR Biological relevance miR-27a 1537Inflammation [24] miR-32-5p 142Inflammation [33] miR-206 2101; 2375Myogenesis [32] List, position, and biological processes of the verified microRNA -binding sites in the 3′UTR of FSTL1 gene In the normal healthy human epidermis, FSTL1 mRNA is expressed, but the protein is present at low to almost undetectable, levels. [score:3]
A list of predicted miRNA -binding sites in the 3′UTR of human FSTL1 with associated clinical relevance is provided in Supplemental Table 1. Table 1 MicroRNA -binding sites in FSTL1 gene Human microRNA Binding position in 3′UTR Biological relevance miR-27a 1537Inflammation [24] miR-32-5p 142Inflammation [33] miR-206 2101; 2375Myogenesis [32] List, position, and biological processes of the verified microRNA -binding sites in the 3′UTR of FSTL1 gene In the normal healthy human epidermis, FSTL1 mRNA is expressed, but the protein is present at low to almost undetectable, levels. [score:3]
MiR-206 is one of the most abundant miRNAs expressed during skeletal myogenesis [116]. [score:3]
This process appears to be mediated by the induction of miR-206 that binds to the 3′UTR of FSTL1 mRNA [32]. [score:1]
Moreover, in silico analysis revealed multiple miRNA -binding sites in the 3′UTR of the FSTL1 mRNA of which three have been functionally analyzed (miR-206 [32], miR-32-5p [33], and miR-27a [24]) (Table  1). [score:1]
[1 to 20 of 6 sentences]
66
[+] score: 16
Subsequent algorithmic and bioinformatic analysis of gene expression databases reveal Fzd7 to be a direct target of miRNA-206 [137]. [score:6]
Goljanek-Whysall K. Pais H. Rathjen T. Sweetman D. Dalmay T. Munsterberg A. Regulation of multiple target genes by miR-1 and miR-206 is pivotal for C2C12 myoblast differentiation J. Cell Sci. [score:4]
Sweetman D. Goljanek K. Rathjen T. Oustanina S. Braun T. Dalmay T. Munsterberg A. Specific requirements of MRFs for the expression of muscle specific microRNAs, miR-1, miR-206 and miR-133 Dev. [score:3]
For instance, miRNA-206 is a critical myogenic regulation factor required for correct skeletal muscle development and differentiation [136]. [score:3]
[1 to 20 of 4 sentences]
67
[+] score: 15
The previous findings that miR-206 regulated ER α expression in breast cancer [22] support the suggestion that miR-206 could be a novel candidate for endocrine therapy to specifically target ER α. Since miR-125a/b was another miRNA involved in HER family -mediated pathway [25], such miRNA could be another target to investigate the mechanism of action of Trastuzumab to the perturbation of signaling pathway in cancer cells. [score:6]
In one study, it is reported that miR-206 expression is significantly downregulated in estrogen receptor alpha (ER α) -positive breast cancer tissues [22]. [score:6]
The potential binding sites of miR-206 was identified in the 3′UTR of human ER α gene [22, 23], suggesting a mutually inhibitory feedback loop between ER α and miR-206. [score:3]
[1 to 20 of 3 sentences]
68
[+] score: 15
Other miRNAs from this paper: hsa-mir-212, hsa-mir-1-2, hsa-mir-122, hsa-mir-132, hsa-mir-1-1
When miR-212-3P and miR-132-3P determined as discussion objects, we firstly analyze the expression of miRNA and its target genes across human tissues, the result provide a sound basis for its involvement in neurological diseases such as epilepsy that miR-132/212 presents brain tissue-specific and elevated expression, there are far more similar example like miR-1/133a and miR-206/133b cluster, known as myomiRs, that suppress key genes in muscle development [15]; the liver-specific miRNA-122* and miR-122 participates extensively in human hepatocellular carcinoma [38, 39]. [score:12]
Such as miR-1/133a and miR-206/133b, which are highly expressed in myocardia and muscle, and are well characterized as muscle-specific miRNAs (myomiRs) that regulate key genes in muscle development [15]. [score:3]
[1 to 20 of 2 sentences]
69
[+] score: 15
MiR-1 and miR-133a are expressed in both skeletal and cardiac muscles [7, 10], while miR-133b and miR-206 are expressed solely in skeletal muscles [10]. [score:5]
Myogenic microRNAs miR-1, miR-133a/b and miR-206 (also called MyomiRs, as suggested by [6]) regulate myogenic differentiation and proliferation of myogenic cells by targeting important regulators of myogenesis [7, 8] (for review see [6, 9]). [score:5]
Human immortalized myoblasts were differentiated in vitro and then transfected separately with anti-miRs targeting miR-1, miR-133a, miR-133b and miR-206. [score:3]
miR-1 and miR-206. [score:1]
[27]-  36 miR-206↑↑enriched in sk. [score:1]
[1 to 20 of 5 sentences]
70
[+] score: 15
Some miRNAs were upregulated 1, 3, and 14 days after infection (miR-15a); others were expressed late (miR-21, miR-206, and miR-451) or transiently upregulated (miR-223), whereas miR-146 was transiently downregulated (Table 1). [score:12]
For instance, miRNA-206 was more highly expressed in infected than in non-infected lungs, while the reverse was reported for trachea. [score:3]
[1 to 20 of 2 sentences]
71
[+] score: 15
The seed mutation of Timp3 miR binding site 1 (pmiR-GLO-Timp3-S1-MUT), but not site 2 (pmiR-GLO-Timp3-S2-MUT), could rescue expression of the reporter gene luciferase, suggesting that site 2 is not involved in the regulation of this gene by miR-1. Limana et al. [26] previously reported that the site 2, but not site 1, was targeted by miR-206, which has identical 5′ seed to miR-1, whilst site 1 did not respond to miR-206 over expression. [score:9]
Interestingly, Timp3 has two predicted binding sites for the miR-1/206 family and despite miR-1 and miR-206 (an already known regulator of Timp3) having identical seed sequences, miR-206 specifically targets the second site [26], while miR-1 specifically targets the first site (Figure 6). [score:6]
[1 to 20 of 2 sentences]
72
[+] score: 14
This particular study examined only downstream genes involved in regulation of lipogenesis, but as LXR is a known regulator of cholesterol-related genes, miR-1 and miR-206 may also be involved in regulation of cholesterol homeostasis through their ability to suppress LXRα and, subsequently, downstream target genes involved in cholesterol synthesis, transport, and uptake (Figure 1a). [score:8]
MiR-1 and miR-206 were also recently shown to suppress LXRα in vitro [38]. [score:3]
Zhong D. Huang G. Zhang Y. Zeng Y. Xu Z. Zhao Y. He X. He F. MicroRNA-1 and microRNA-206 suppress LXRα -induced lipogenesis in hepatocytes Cell. [score:3]
[1 to 20 of 3 sentences]
73
[+] score: 14
Kondo et al reported that miR-206 was markedly decreased in ERα -positive human breast cancer tissues and that the introduction of miR-206 into estrogen -dependent MCF-7 breast cancer cells led to the suppression of ERα expression and growth inhibition (9). [score:7]
Leivonen et al previously reported that five ERα -regulating miRNAs, miR-18a, miR-18b, miR-193b, miR-302c and miR-206, directly targeted ERα in 3’UTR reporter assays (11). [score:4]
Adams et al identified that miR-206 decreases endogenous ERα mRNA and protein levels in MCF-7 cells by acting through two specific miR-206 target sites within the 3’UTR of the human ERα transcript (10). [score:3]
[1 to 20 of 3 sentences]
74
[+] score: 14
Conversely, up-regulation of Bcl2 was confirmed in human lung cancer tissue samples, inversely correlated with miR-206 expression and validated miR-206 binding sites are present within the 3′-untranslated region (3′-UTR) of Bcl2 [59]. [score:8]
The expression of Bcl2 has been shown to be down-regulated after treatment with miR-206 [59]. [score:6]
[1 to 20 of 2 sentences]
75
[+] score: 14
Downregulation of microRNA-206 has been reported in breast carcinoma, leiomyoma, lung carcinoma, renal cell carcinoma, and rhabdomyosarcomas [113– 117]. [score:4]
Zhang et al. demonstrated that the expression levels of miR-206 are associated with the T grade, nodal metastasis and clinical stage of patients with laryngeal carcinoma [118]. [score:3]
In laryngeal carcinoma tissues, microRNA-206 expression was significantly reduced in comparison with the normal laryngeal tissues [118, 119]. [score:3]
Taken together, miR-206 is suggested to be a candidate tumor-suppressing microRNA in human cancers. [score:3]
Liu et al. show that miR-206 controls cell migration and invasion through modulating the actin cytoskeleton [121]. [score:1]
[1 to 20 of 5 sentences]
76
[+] score: 13
Other miRNAs from this paper: mmu-mir-137, mmu-mir-206, hsa-mir-137
Interestingly, ER1 is expressed in the mesenchyme surrounding the mammary bud at E12.5 [5] and is a target of miR-206, which is also expressed in the mesenchyme at E11.5 and E12.5 (earlier than miR-137) but not at E13.5 [35]. [score:7]
When miR-206 was over-expressed in the same flank culture system used here, mammary placode development was very severely retarded; the placode formed but did not thicken [35]. [score:4]
This is consistent with miR-206 having a function at a slightly earlier stage in mammary gland development than miR-137. [score:2]
[1 to 20 of 3 sentences]
77
[+] score: 13
Accumulating evidences further indicate that numerous miRNAs can impede cancer progression via direct suppression of VEGF-C. miR-27b, miR-101, miR-128, miR-206 and miR-1826 have been reported to inhibit tumor growth, lymphangiogenesis and metastasis by targeting VEGF-C in a variety of human cancer cells [20– 22, 38– 40]. [score:8]
miR-206 also abrogates the expression and secretion of VEGF-C, and subsequently inhibits tumor lymphangiogenesis in pancreatic cancer [21]. [score:5]
[1 to 20 of 2 sentences]
78
[+] score: 13
Other miRNAs from this paper: hsa-mir-22, hsa-mir-29a, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-146a
This has, for example, been shown in amyotrophic lateral sclerosis (ALS), where upregulation of miR-206 has been shown to be part of a cellular autocompensatory mechanism by promoting regeneration at neuromuscular synapses and slowing ALS progression through the downregulation of HDAC4 expression [9]. [score:9]
For example, upregulation of miR-206 has been shown to slow the progression of neurodegeneration in a mouse mo del of amyotrophic lateral sclerosis by promoting regeneration of neuromuscular synapses [9]. [score:4]
[1 to 20 of 2 sentences]
79
[+] score: 13
They showed up-regulation of the expressions of miR-204 and miR-206 and down-regulation of miR-9, miR-100, miR-223, and miR-200c in CD133 [+] cells using RT PCR. [score:9]
Guo and colleagues reported that the expression levels of miR-204, miR-206, miR-223, miR-9, miR-100, and miR-200c were dysregulated in CD133 [+] OVCAR3 human ovarian cancer cells [12]. [score:4]
[1 to 20 of 2 sentences]
80
[+] score: 13
DND1 has also been shown to inhibit miR-372 from the 3′-UTRs of LATS2 (serine/threonine-protein kinase, large tumor suppressor, homolog 2) and inhibit miR-1 and miR-206 from the 3′-UTRs of CX43 (connexin-43) [4]. [score:7]
APOBEC3G had a similar effect of blocking DND1 function to restore miR-206 inhibition from CX43 (connexin-43; pGL3 Cx43 3′UTR) (P = 0.02) and to restore miR-372 inhibition from the 3′-UTR of LATS2 (pGL3 3′UTR LATS2) (P = 0.001) (Figure  1d and 1e). [score:5]
Similar transfections also tested the effect of DND1, APOBEC3G and miR-372 (mirVec-372) on pGL3 3′UTR LATS2, and miR-206 (miR vec-206) on pGL3 Cx43 3′UTR and pGL3-control vector. [score:1]
[1 to 20 of 3 sentences]
81
[+] score: 13
This is particularly noticeable after day 8 where miR-206 expression suddenly jumps and ANP32B expression drops. [score:5]
In this case the players are ANP32B, a histone chaperone and negative regulator for apoptosis [43], and miR-206, a miRNA known to be involved in myogenesis and to regulate the expression of other histone modifying genes [44], [45]. [score:5]
As with ITGB1, the H3K4me [3] levels around the ANP32B TSS show little or no correlation with ANP32B expression levels, but strong anti-correlation with miR-206. [score:3]
[1 to 20 of 3 sentences]
82
[+] score: 13
Other miRNAs from this paper: mmu-mir-206
[18] Indeed, in lapatinib -treated cells the elevated KLF4 was associated with increased levels of miR-206, which can then directly target the KLF4 3' UTR (Figure 3e, right panel). [score:4]
[18] This decrease is expected when KLF4 transcriptional activity is elevated, attributed to a well-characterized negative feedback signal by which KLF4 induces miR-206 and suppresses its own translation. [score:3]
Nevertheless, the results indicate that lapatinib treatment of HER2 -positive breast cancer cells can enhance KLF4 protein expression and its transcriptional activity as indicated by miR-206 levels. [score:3]
2, 55 Despite these results, and the clear dependence of MCL1 on KLF4/5 expression (Figures 5b and c), the MCL1 locus was not enriched in KLF4/5 ChIP assays, in which MIR206 served as a positive control (data not shown). [score:2]
In response to deficient RTK signaling, KLF4/5 can coordinate a prosurvival response that includes BCL2 family proteins, miR-206 and likely other factors. [score:1]
[1 to 20 of 5 sentences]
83
[+] score: 12
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-101-1, hsa-mir-106a, hsa-mir-107, hsa-mir-16-2, hsa-mir-192, hsa-mir-196a-1, hsa-mir-199a-1, hsa-mir-129-1, hsa-mir-148a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-196a-2, hsa-mir-199a-2, hsa-mir-203a, hsa-mir-210, hsa-mir-212, hsa-mir-214, hsa-mir-215, hsa-mir-217, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-129-2, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-195, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-200a, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-130b, hsa-mir-376c, hsa-mir-375, hsa-mir-378a, hsa-mir-148b, hsa-mir-338, hsa-mir-335, hsa-mir-423, hsa-mir-20b, hsa-mir-429, hsa-mir-449a, hsa-mir-433, hsa-mir-451a, hsa-mir-193b, hsa-mir-520d, hsa-mir-503, hsa-mir-92b, hsa-mir-610, hsa-mir-630, hsa-mir-650, hsa-mir-449b, hsa-mir-421, hsa-mir-449c, hsa-mir-378d-2, hsa-mir-744, hsa-mir-1207, hsa-mir-1266, hsa-mir-378b, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-4512, hsa-mir-378i, hsa-mir-203b, hsa-mir-451b, hsa-mir-378j
Moreover, GC patients with over -expression of miR-107 [28, 29, 30], miR-143 [40], miR-145 [41, 42], miR-181b/c [17, 47, 48, 55, 56], miR-196a/b [59], miR-20b [23, 66], miR-23a/b [77, 78, 79], miR-34 [17, 47, 48, 55, 56] and miR-630 [100] and decreased expression of miR-1 [111], miR-1207-5p [121], miR-125a-3p/-5p [24, 125, 126, 127], miR-185 [140], miR-193b [60], miR-20a [111], miR-206 [150, 151], miR-215 [142], miR-217 [153], miR-27a [111], miR-29c [169], miR-34a [172, 173], miR-423-5p [111], and miR-520d-3p [99] indicate advanced tumor stage or TNM stage. [score:5]
Yang Q. Zhang C. Huang B. Li H. Zhang R. Huang Y. Wang J. Downregulation of microRNA-206 is a potent prognostic marker for patients with gastric cancer Eur. [score:4]
Zhang L. Liu X. Jin H. Guo X. Xia L. Chen Z. Bai M. Liu J. Shang X. Wu K. miR-206 inhibits gastric cancer proliferation in part by repressing cyclinD2 Cancer Lett. [score:3]
[1 to 20 of 3 sentences]
84
[+] score: 12
Development of cardiovascular disease is associated with up-regulation of miR-206 (Shan et al. 2009), and this miRNA has significantly higher expression levels in smokers than in nonsmokers. [score:9]
Biomed Res Int 758323; 10.1155/2014/758323 Gambar della S Rinaldi F Lepore SM Viola A Loro E Angelini C 2010 Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients. [score:3]
[1 to 20 of 2 sentences]
85
[+] score: 12
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-27a, hsa-mir-92a-1, hsa-mir-92a-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-15b, mmu-mir-23b, mmu-mir-27b, mmu-mir-130a, mmu-mir-133a-1, mmu-mir-140, mmu-mir-24-1, hsa-mir-196a-1, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-206, hsa-mir-30c-2, hsa-mir-196a-2, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-200b, mmu-mir-301a, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-130a, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-140, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-196a-1, mmu-mir-196a-2, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-18a, mmu-mir-20a, mmu-mir-24-2, mmu-mir-27a, mmu-mir-92a-2, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-17, mmu-mir-19a, mmu-mir-200c, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-19b-1, mmu-mir-92a-1, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-301a, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, hsa-mir-196b, mmu-mir-196b, dre-mir-196a-1, dre-mir-199-1, dre-mir-199-2, dre-mir-199-3, hsa-mir-18b, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-1-2, dre-mir-1-1, dre-mir-15a-1, dre-mir-15a-2, dre-mir-15b, dre-mir-17a-1, dre-mir-17a-2, dre-mir-18a, dre-mir-18b, dre-mir-18c, dre-mir-19a, dre-mir-20a, dre-mir-23b, dre-mir-24-4, dre-mir-24-2, dre-mir-24-3, dre-mir-24-1, dre-mir-27a, dre-mir-27b, dre-mir-27c, dre-mir-27d, dre-mir-27e, dre-mir-30c, dre-mir-92a-1, dre-mir-92a-2, dre-mir-92b, dre-mir-130a, dre-mir-133a-2, dre-mir-133a-1, dre-mir-133b, dre-mir-133c, dre-mir-140, dre-mir-196a-2, dre-mir-196b, dre-mir-200a, dre-mir-200b, dre-mir-200c, dre-mir-206-1, dre-mir-206-2, dre-mir-301a, dre-let-7j, hsa-mir-92b, mmu-mir-666, mmu-mir-18b, mmu-mir-92b, mmu-mir-1b, dre-mir-196c, dre-mir-196d, mmu-mir-3074-1, mmu-mir-3074-2, hsa-mir-3074, mmu-mir-133c, mmu-let-7j, mmu-let-7k, dre-mir-24b
MIR-206 regulates connexin43 expression during skeletal muscle development. [score:5]
Further, like the comparison between MiR23b and MiR24.1, expression of MiR206 was much weaker than the expression observed for MiR133b. [score:4]
Like Mir23b, Mir133b exists in a cluster with Mir206, which had a similar pattern of expression to that of Mir133b. [score:2]
Muscle-specific microRNA miR-206 promotes muscle differentiation. [score:1]
[1 to 20 of 4 sentences]
86
[+] score: 12
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-92a-1, hsa-mir-93, hsa-mir-98, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-196a-1, hsa-mir-197, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-182, hsa-mir-183, hsa-mir-196a-2, hsa-mir-205, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-137, hsa-mir-140, hsa-mir-141, hsa-mir-143, hsa-mir-145, hsa-mir-152, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-146a, hsa-mir-150, hsa-mir-194-1, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-200a, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-26a-2, hsa-mir-372, hsa-mir-374a, hsa-mir-375, hsa-mir-328, hsa-mir-133b, hsa-mir-20b, hsa-mir-429, hsa-mir-449a, hsa-mir-486-1, hsa-mir-146b, hsa-mir-494, hsa-mir-503, hsa-mir-574, hsa-mir-628, hsa-mir-630, hsa-mir-449b, hsa-mir-449c, hsa-mir-708, hsa-mir-301b, hsa-mir-1827, hsa-mir-486-2
In lung tumors, miR-206 expression levels were markedly lower in highly metastatic forms than in low metastatic tumors and normal lung tissues, and its upregulation causes the induction of apoptosis, the inhibition of lung cancer cell proliferation, migration and invasion [149]. [score:8]
MiR-133 and miR-206 have been termed “muscle specific” miRNAs since they are highly expressed in cardiac and smooth muscle tissues [149- 150]. [score:3]
miR-133, miR-206. [score:1]
[1 to 20 of 3 sentences]
87
[+] score: 11
The expression levels of 12 miRNAs, including miR-139-3p, miR-204, miR-760, miR-432, miR-524-5p, miR-136, miR-548d-3p, miR-206, miR-214, miR-383, miR-224, and miR-887 were significantly lower, whereas the expression level of miR-146a was significantly higher, in Jurkat cells after being cultured with TNF-α for 7 days (fold change > 4, p < 0.05, Fig.   1b). [score:5]
Decreased expression of miR-206 in Jurkat cells after chronic exposure to TNF-α was also noted in our study. [score:3]
Among them, decreased expression of miR-206 was noted in myogenic cells, and can potentially affect MAPK pathways [9]. [score:3]
[1 to 20 of 3 sentences]
88
[+] score: 11
miR-206 regulates the growth of the teleost tilapia (Oreochromis niloticus) through the modulation of IGF-1 gene expression. [score:4]
Hou et al. [40] showed that ssc-miR-206, ssc-miR-378, and ssc-miR-1 were expressed at extremely high levels in the longissimus dorsi muscles of Tong Cheng pigs. [score:3]
For example, muscle-specific miRNAs (myomiRs), such as miR-1, miR-133a/b, miR-206, and miR-486, were shown to be involved in the regulation of skeletal muscle hypertrophy by modulating the IGF-1–Akt pathway and myostatin signaling pathway [13– 17]. [score:2]
The most abundant miRNA was ssc-miR-206, which was present by more than 4,600,000 TP5M in ten libraries. [score:1]
In the present study, we found that ssc-miR-206, ssc-miR-378, and ssc-miR-1 were ranked 1 [st], 3 [rd], and 4 [th] in abundance among the ten libraries, which is consistent with the previous study. [score:1]
[1 to 20 of 5 sentences]
89
[+] score: 11
Kondo N. Toyama T. Sugiura H. Fujii Y. Yamashita H. miR-206 expression is down-regulated in estrogen receptor α -positive human breast cancer Cancer Res. [score:6]
Adams B. D. Furneaux H. White B. A. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-α (ERα) and represses ERα messenger RNA and protein expression in breast cancer cell lines Mol. [score:5]
[1 to 20 of 2 sentences]
90
[+] score: 11
Other miRNAs from this paper: hsa-mir-223, hsa-mir-150
[46] Several mechanisms regulating Notch3 expression have been recently reported: miRNA-206 has been shown to inhibit colon cancer cell proliferation and migration through direct Notch3 targeting, [47] as well as mir-150 does to regulate T-cell development. [score:11]
[1 to 20 of 1 sentences]
91
[+] score: 11
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-27a, hsa-mir-29a, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-148a, hsa-mir-10a, hsa-mir-181a-2, hsa-mir-181c, hsa-mir-199a-2, hsa-mir-181a-1, hsa-mir-214, hsa-mir-221, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-23b, hsa-mir-27b, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-143, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-1-1, hsa-mir-128-2, hsa-mir-29c, hsa-mir-26a-2, hsa-mir-378a, hsa-mir-148b, hsa-mir-133b, hsa-mir-424, ssc-mir-125b-2, ssc-mir-148a, ssc-mir-23a, ssc-mir-24-1, ssc-mir-26a, ssc-mir-29b-1, ssc-mir-181c, ssc-mir-214, ssc-mir-27a, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-103-1, ssc-mir-128-1, ssc-mir-29c, hsa-mir-486-1, hsa-mir-499a, hsa-mir-503, hsa-mir-411, hsa-mir-378d-2, hsa-mir-208b, hsa-mir-103b-1, hsa-mir-103b-2, ssc-mir-17, ssc-mir-221, ssc-mir-133a-1, ssc-mir-1, ssc-mir-503, ssc-mir-181a-1, ssc-mir-206, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-378-1, ssc-mir-133b, ssc-mir-29a, ssc-mir-199a-2, ssc-mir-128-2, ssc-mir-499, ssc-mir-143, ssc-mir-10a, ssc-mir-486-1, ssc-mir-103-2, ssc-mir-181a-2, ssc-mir-27b, ssc-mir-24-2, ssc-mir-23b, ssc-mir-148b, ssc-mir-208b, ssc-mir-424, ssc-mir-127, ssc-mir-125b-1, hsa-mir-378b, hsa-mir-378c, ssc-mir-411, ssc-mir-133a-2, ssc-mir-126, ssc-mir-199a-1, ssc-mir-378-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-499b, ssc-let-7a-2, ssc-mir-486-2, hsa-mir-378j, ssc-let-7d, ssc-let-7f-2, ssc-mir-29b-2, hsa-mir-486-2, ssc-mir-378b
MiR-127, which is located within a CpG island with little research on myogenesis, showed similar expression pattern to ssc-miR-206, up regulated at 35 to 77 dpc and down regulated at 77 dpc to 180 dpn (Figure 5B), providing the possibility for further investigation concerning the function of ssc-miR-127 during muscle development. [score:4]
Similarly, two other myomiRs, miR-133 [21] and miR-206 [23], were highly expressed and ranked the 4 [th] and 6 [th] respectively, while two other miRNAs (miR-378 [24, 25] and miR-143 [25]) ranked the 2 [nd] and 3 [rd] have been identified to participate in the proliferation and differentiation of muscle cells. [score:3]
It’s worth noting that many miRNAs are expressed in a tissue-specific or stage-specific manner [10], and the best-characterized muscle-specific miRNAs (myomiRs [11]) are miR-1, miR-206 and miR-133 families which specifically expressed in cardiac and skeletal muscles. [score:3]
However, Cluster 5 illustrated that ssc-miR-206 and other four muscle-related miRNAs (ssc-miR-126, -148a/b and -15b) continued to decline while ssc-miR-133b and eleven other muscle-related miRNAs (ssc-miR-125b, -128,-181a/b, -199a, -214, -23a, -24, -424, -503 and -7) in Cluster 4 presented a down and then up trend from 77 dpc to 180 dpn, suggesting their different roles played in adult fiber maturation. [score:1]
[1 to 20 of 4 sentences]
92
[+] score: 11
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-17, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-16-2, mmu-mir-23b, mmu-mir-27b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-127, mmu-mir-128-1, mmu-mir-132, mmu-mir-133a-1, mmu-mir-188, mmu-mir-194-1, mmu-mir-195a, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-205, mmu-mir-206, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-122, mmu-mir-30e, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-205, hsa-mir-211, hsa-mir-212, hsa-mir-214, hsa-mir-217, hsa-mir-200b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-128-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-127, hsa-mir-138-1, hsa-mir-188, hsa-mir-194-1, hsa-mir-195, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-23a, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-31, mmu-mir-351, hsa-mir-200c, mmu-mir-17, mmu-mir-19a, mmu-mir-100, mmu-mir-200c, mmu-mir-212, mmu-mir-214, mmu-mir-26a-2, mmu-mir-211, mmu-mir-29b-2, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-19b-1, mmu-mir-138-1, mmu-mir-128-2, hsa-mir-128-2, mmu-mir-217, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-379, mmu-mir-379, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-412, mmu-mir-431, hsa-mir-431, hsa-mir-451a, mmu-mir-451a, mmu-mir-467a-1, hsa-mir-412, hsa-mir-485, hsa-mir-487a, hsa-mir-491, hsa-mir-503, hsa-mir-504, mmu-mir-485, hsa-mir-487b, mmu-mir-487b, mmu-mir-503, hsa-mir-556, hsa-mir-584, mmu-mir-665, mmu-mir-669a-1, mmu-mir-674, mmu-mir-690, mmu-mir-669a-2, mmu-mir-669a-3, mmu-mir-669c, mmu-mir-696, mmu-mir-491, mmu-mir-504, hsa-mir-665, mmu-mir-467e, mmu-mir-669k, mmu-mir-669f, hsa-mir-664a, mmu-mir-1896, mmu-mir-1894, mmu-mir-1943, mmu-mir-1983, mmu-mir-1839, mmu-mir-3064, mmu-mir-3072, mmu-mir-467a-2, mmu-mir-669a-4, mmu-mir-669a-5, mmu-mir-467a-3, mmu-mir-669a-6, mmu-mir-467a-4, mmu-mir-669a-7, mmu-mir-467a-5, mmu-mir-467a-6, mmu-mir-669a-8, mmu-mir-669a-9, mmu-mir-467a-7, mmu-mir-467a-8, mmu-mir-669a-10, mmu-mir-467a-9, mmu-mir-669a-11, mmu-mir-467a-10, mmu-mir-669a-12, mmu-mir-3473a, hsa-mir-23c, hsa-mir-4436a, hsa-mir-4454, mmu-mir-3473b, hsa-mir-4681, hsa-mir-3064, hsa-mir-4436b-1, hsa-mir-4790, hsa-mir-4804, hsa-mir-548ap, mmu-mir-3473c, mmu-mir-5110, mmu-mir-3473d, mmu-mir-5128, hsa-mir-4436b-2, mmu-mir-195b, mmu-mir-133c, mmu-mir-30f, mmu-mir-3473e, hsa-mir-6825, hsa-mir-6888, mmu-mir-6967-1, mmu-mir-3473f, mmu-mir-3473g, mmu-mir-6967-2, mmu-mir-3473h
MiR-206, miR-133, miR-199, miR-100 and miR-195 were implicated in the autophagy pathway targeting BCL2, MTOR and SQSTM1 as possible autophagy gene targets (Table 6). [score:5]
Furthermore, the pathway analysis links a group of miRNAs that were differentially expressed in cbs [+/–] retina to oxidative stress pathway such as miR-205, miR-206, miR-217, miR-30, miR-27, miR-214 and miR-3473. [score:3]
Consistently with the microarray results, miR-205 (p value = 0.001), miR-206 (p value = 0.01) and miR-27 (p value = 0.04) were significantly downregulated in cbs [+/–] compared to control cbs [+/+] (p value < 0.05). [score:3]
[1 to 20 of 3 sentences]
93
[+] score: 11
miR-206 has been suggested to function as an inflammatory regulator leading to the expression of MMP9 by targeting TIMP3 in Mtb infection (Fu et al., 2016). [score:6]
MicroRNA-206 regulates the secretion of inflammatory cytokines and MMP9 expression by targeting TIMP3 in Mycobacterium tuberculosis–infected THP-1 human macrophages. [score:5]
[1 to 20 of 2 sentences]
94
[+] score: 10
Other miRNAs from this paper: hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-21, hsa-mir-23a, hsa-mir-100, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, mmu-mir-1a-1, mmu-mir-23b, mmu-mir-125b-2, mmu-mir-130a, mmu-mir-9-2, mmu-mir-145a, mmu-mir-181a-2, mmu-mir-184, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-205, mmu-mir-206, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-199a-2, hsa-mir-205, hsa-mir-181a-1, hsa-mir-214, hsa-mir-219a-1, hsa-mir-223, mmu-mir-302a, hsa-mir-1-2, hsa-mir-23b, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-184, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-21a, mmu-mir-23a, mmu-mir-103-1, mmu-mir-103-2, rno-mir-338, mmu-mir-338, rno-mir-20a, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-107, mmu-mir-17, mmu-mir-100, mmu-mir-181a-1, mmu-mir-214, mmu-mir-219a-1, mmu-mir-223, mmu-mir-199a-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-181b-1, mmu-mir-125b-1, hsa-mir-302a, hsa-mir-219a-2, mmu-mir-219a-2, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, hsa-mir-372, hsa-mir-338, mmu-mir-181b-2, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-16, rno-mir-17-1, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-100, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-125b-1, rno-mir-125b-2, rno-mir-130a, rno-mir-145, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-184, rno-mir-199a, rno-mir-205, rno-mir-206, rno-mir-181a-1, rno-mir-214, rno-mir-219a-1, rno-mir-219a-2, rno-mir-223, hsa-mir-512-1, hsa-mir-512-2, rno-mir-1, mmu-mir-367, mmu-mir-302b, mmu-mir-302c, mmu-mir-302d, rno-mir-17-2, hsa-mir-1183, mmu-mir-1b, hsa-mir-302e, hsa-mir-302f, hsa-mir-103b-1, hsa-mir-103b-2, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, rno-mir-219b, hsa-mir-23c, hsa-mir-219b, mmu-mir-145b, mmu-mir-21b, mmu-mir-21c, mmu-mir-219b, mmu-mir-219c, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
For instance, TPPP/p25 is a potential target for several miRNAs, including miR-1. Thus, an increase in one miRNA such as miR-206 may not be sufficient to significantly repress the expression of this protein. [score:5]
Conversely, another study demonstrated that the absence of miR-206 was essential for OL differentiation from rat bipotential oligodendrocyte-type 2-astrocyte (O-2A) progenitor cells which have the capability of generating both oligodendrocytes and astrocytes by targeting the tubilin polymerization-promoting protein (TPPP/p25), a marker of myelinating oligodendrocytes [21]. [score:3]
It is also not known whether these results are due to differences in rat and human, or whether the absence of miRNA-206 is only required for the initiation of the TPPP/p25 pathway prior to myelination. [score:1]
Our results also demonstrate a progressive decrease in miR-206 during ESC-derived OL differentiation. [score:1]
[1 to 20 of 4 sentences]
95
[+] score: 10
Increasing evidence suggests that several miRNAs can reduce tumor progression via direct repression of VEGF-A. miR-199a, miR-200b, miR-206, miR-210, and miR-374b have been shown to inhibit metastasis and angiogenesis in several human cancer cells by targeting VEGF-A [18, 25, 38, 39]. [score:6]
For example, miR-199a has been shown to reduce angiogenesis in chondrosarcoma cells by directly inhibiting VEGF-A production [18], while miR-206 diminishes the production of VEGF-A, subsequently reducing cancer angiogenesis in renal carcinoma [19]. [score:4]
[1 to 20 of 2 sentences]
96
[+] score: 10
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-98, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-210, hsa-mir-215, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-143, hsa-mir-144, hsa-mir-145, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-138-1, hsa-mir-146a, hsa-mir-193a, hsa-mir-194-1, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-302a, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-369, hsa-mir-371a, hsa-mir-340, hsa-mir-335, hsa-mir-133b, hsa-mir-146b, hsa-mir-519e, hsa-mir-519c, hsa-mir-519b, hsa-mir-519d, hsa-mir-519a-1, hsa-mir-519a-2, hsa-mir-499a, hsa-mir-504, hsa-mir-421, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-190b, hsa-mir-301b, hsa-mir-302e, hsa-mir-302f, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-320e, hsa-mir-371b, hsa-mir-499b
Shan Z. X. Lin Q. X. Fu Y. H. Deng C. Y. Zhou Z. L. Zhu J. N. Liu X. -Y. Zhang Y. -Y. Li Y. Lin S. -G. Upregulated expression of miR-1/miR-206 in a rat mo del of myocardial infarction Biochem. [score:6]
MicroRNA miR-1 has also been documented to directly target IGF1 transcripts in cardiac and skeletal muscle [72], as have miR-320 and miR-206 in a rat mo del of myocardial infarction [73]. [score:4]
[1 to 20 of 2 sentences]
97
[+] score: 10
Other miRNAs from this paper: hsa-mir-134, hsa-mir-326, hsa-mir-329-1, hsa-mir-329-2
Ectopic expression of miR-326, miR-134, miR-329, and miR-206 in NSCLC cell lines significantly suppressed cell proliferation through inhibition of cyclin D1 and up-regulation p21 [37– 40]. [score:10]
[1 to 20 of 1 sentences]
98
[+] score: 10
Increasing evidence suggests that several miRNAs can reduce tumor progression via direct repression of VEGF-C. miR-27b, miR-101, miR-128 and miR-206 have been shown to inhibit lymphangiogenesis and metastasis in a variety of human cancer cells, via the targeting of VEGF-C. 27, 37, 38 This current study demonstrates that BDNF markedly inhibited the expression of miR-624-3p in human chondrosarcoma cells and specimens. [score:10]
[1 to 20 of 1 sentences]
99
[+] score: 10
ERα expression promotes the differentiation of mammary epithelial cells and opposes EMT: thus, a loss of ERα expression, e. g., by upregulation of miR-206 that targets ERα, is associated with EMT [17]. [score:10]
[1 to 20 of 1 sentences]
100
[+] score: 10
human primary differentiated keratinocytes and differentiation-inducible RD18 cells carrying a doxycycline-inducible miR-206 -expressing lentiviral vector in the absence (uninduced: NI) or presence of doxycycline for four (induced: IND4) and six days (induced: IND6). [score:3]
The RD18 NpBI-206 cells carry a doxycycline-inducible miR-206 -expressing lentiviral vector [16]. [score:3]
Thus, we evaluated VDR expression levels in two mo dels, allowing for the examination of human proliferating cells and their differentiated counterparts: We compared HaCaT proliferating keratinocyte cells to fully differentiated primary keratinocytes and rhabdomyosarcoma RD18 cells that had been induced to differentiate by the conditional expression of miR-206 [16]. [score:2]
We observed decreased mitochondrial VDR levels in two different mo dels of differentiated cells (primary cultures of keratinocytes represent physiological differentiation, whereas miR-206 -induced RD18 cells represent an miRNA -driven differentiated state). [score:1]
For the differentiation experiments, the cells were constantly maintained in high serum-containing media (10% FBS) in the presence or absence of doxycycline (1 µg/ml) for the indicated number of days (induced miR-206, IND; uninduced miR-206, NI). [score:1]
[1 to 20 of 5 sentences]