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15 publications mentioning mmu-mir-543

Open access articles that are associated with the species Mus musculus and mention the gene name mir-543. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 442
Other miRNAs from this paper: mmu-mir-200b
Data were expressed as log2 fold change (relative miR-543 expression in tumor sample/relative miR-543 expression in matched normal colon tissue) to show the relative expression in every paired samples (A) and the relative expression difference between all normal colon samples and tumor samples (B). [score:11]
Figure 4miR-543 overexpression suppresses the migration and invasion of CRC cells in vitro and re -expression of KRAS, MTA1 and HMGA2 reverses the miR-543 -induced effects on CRC cells(A) Transwell migration assays revealed that ectopic overexpression of miR-543 inhibits the migration ability of SW620 and LoVo cells. [score:10]
miR-543 overexpression inhibits tumor growth and metastasis of CRC cells in vivoAfter determining that miR-543 overexpression significantly suppresses the proliferation, migration and invasion of CRC cells in vitro, we further investigated whether miR-543 could inhibit the growth and metastasis of CRC cells in vivo. [score:9]
Therefore, these results support the notion that the downregulation of miR-543 in CRC cells “contributes to the activation of multiple oncogenic signaling” pathways by upregulating the expression of KRAS, MTA1 and HMGA2, and ultimately results in CRC progression and metastasis. [score:9]
To this end, we stably knocked down the expression of miR-543 in HCT116 cells, which has relatively high endogenous miR-543 expression, using a lentivirus -based antagomir expression system (Supplementary Figure S7) [31]. [score:8]
Relative miR-543 expression (T/N) was 0.86 in one paired samples and this paired samples was considered to be a case with high miR-543 expression, whereas another paired samples whose relative miR-543 expression was 0.30 was regarded as a case with low miR-543 expression. [score:8]
Strikingly, exogenous expression of these three target genes almost completely rescued the miR-543 -induced inhibitory effects on cell proliferation (Figure 4F) and colony formation (Supplementary Figure S4). [score:7]
To abrogate the suppression of miR-543 on KRAS, MTA1 and HMGA2, plasmids expressing each target gene lacking a 3′UTR were constructed and transduced into LoVo-miR-543 cells (Figure 4E). [score:7]
To explore the tumor-suppressive roles of miR-543 in CRC, we further examined the putative downstream targets of miR-543 by three in silico prediction algorithms (miRanda, TargetScan and miRWalk). [score:7]
Quantitative immunohistochemical staining results revealed that CRC tissues with a high level of miR-543 had low expression of KRAS, MTA1 and HMGA2, whereas CRC tissues with a low level of miR-543 exhibited high expression of KRAS, MTA1 and HMGA2, indicating that miR-543 expression is inversely correlated with the levels of KRAS, MTA1 and HMGA2 in clinical CRC tissues (Figure 7). [score:7]
miR-543 overexpression suppresses the migration and invasion of CRC cells in vitro and re -expression of KRAS, MTA1 and HMGA2 reverses the miR-543 -induced effects on CRC cells. [score:7]
Therefore, re -expression of KRAS, MTA1 or HMGA2 reverses the miR-543 -induced inhibition of the proliferation, migration and invasion of CRC cells in vitro, indicating that KRAS, MTA1 and HMGA2 are functional targets of miR-543 in CRC cells. [score:7]
Moreover, miR-543 overexpression inhibits the growth and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. [score:7]
Consistent with these phenotypes, the mRNA levels of KRAS and Cyclin D1 and the protein levels of KRAS, p-MEK, p-ERK and Cyclin D1 upregulated when endogenous miR-543 was suppressed (Figure 6C and 6D). [score:6]
In conclusion, our study highlights a pivotal role for miR-543 as a tumor suppressor in the regulation of CRC cell proliferation and metastasis by targeting KRAS, MTA1 and HMGA2 and suggests that miR-543 may serve as a novel diagnostic and prognostic biomarker for CRC metastasis. [score:6]
miR-543 expression is downregulated in CRC tissues and inversely correlated with CRC metastasis. [score:6]
miR-543 expression is downregulated in clinical colorectal cancer (CRC) samples, CRC cell lines and mouse CRC tissues. [score:6]
In this study, we report that the expression of miR-543 is significantly downregulated in human and mouse CRC tissues and is inversely correlated with the N classification and metastatic status of patients with CRC. [score:6]
Next, we performed rescue experiments to further confirm that miR-543 inhibits the malignant phenotypic alterations of CRC cells by directly repressing the three target genes. [score:6]
Together, these results indicate that miR-543 may inhibit the proliferation of CRC cells by downregulating the KRAS-related oncogenic pathway. [score:6]
Figure 3miR-543 overexpression inhibits the proliferation of CRC cells in vitro(A, B) MTT analysis of the effects of miR-543 on the proliferation of SW620-Ctrl and SW620-miR-543 (A) and LoVo-Ctrl and LoVo-miR-543 cells (B). [score:5]
miR-543 overexpression inhibits the tumor growth and metastasis of CRC cells in vivo. [score:5]
After determining that miR-543 overexpression significantly suppresses the proliferation, migration and invasion of CRC cells in vitro, we further investigated whether miR-543 could inhibit the growth and metastasis of CRC cells in vivo. [score:5]
Upon ectopic overexpression of miR-543, we did not observe significant alterations of the epithelial cell markers E-cadherin and β-catenin or the mesenchymal cell markers N-cadherin and Vimentin in SW620 and LoVo cells (Supplementary Figure S2), indicating that the miR-543-related inhibition of cell migration and invasion is dependent on mechanisms other than EMT. [score:5]
These data indicate that miR-543 suppresses CRC invasion in vitro by targeting MTA1 and HMGA2. [score:5]
miR-543 overexpression inhibits the proliferation of CRC cells in vitro. [score:5]
The 2 [−ΔΔCt] (ΔCt = CtmiR-543-CtU6) method for quantitation of gene expression was used to determine miR-543 relative expression levels. [score:5]
The mean relative miR-543 expression (5.8) of all clinical tumor samples was chosen as the cut-off to classify a tumor sample was High or Low according to their miR-543 expression level. [score:5]
Moreover, restoration of KRAS, MTA1 or HMGA2 in CRC cells at least partially reversed the inhibitory effects on cell migration imposed by miR-543 expression (Figure 4G; Supplementary Figure S5). [score:5]
We next examined whether miR-543 could suppress the motility and invasiveness of CRC cells by targeting MTA1 and HMGA2. [score:5]
The KRAS-RAF-MEK-ERK-Cyclin D1 signaling pathway is a key promoter of the CRC malignant process through its effects on cell proliferation [20, 21]; thus, we next determined whether miR-543 inhibits CRC cell proliferation by targeting KRAS. [score:5]
Similarly, stable expression of miR-543 inhibited the tumor growth of LoVo cells in vivo (Figure 5B). [score:5]
SW620, LoVo and their miR-543 -overexpressing cells, which also expressed the luciferase gene, were intrasplenically injected into nude mice to develop experimental intestinal and hepatic metastasis. [score:5]
Figure 5miR-543 overexpression inhibits the tumor growth and metastasis of CRC cells in vivo(A) Bioluminescence images of nude mice showing tumors derived 28 days after subcutaneous injection in the lower back regions of nude mice with SW620-Ctrl or SW620-miR-543 cells (left). [score:5]
Here, we found that miR-543 overexpression in SW620 and LoVo cells increased the level of miR-200b but decreased the expression of HMGA2 and LOX at the mRNA (Figure 4C) and protein levels (Figure 4D). [score:5]
We demonstrate that miR-543 inhibits the growth and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. [score:5]
Here, our data reveal that there is an inverse correlation between the miR-543 level and the expression of its targets, KRAS, MTA1 and HMGA2, in clinical CRC samples. [score:5]
As shown in Figure 3E, overexpression of miR-543 in SW620 and LoVo cells decreased the expression of KRAS and Cyclin D1 at the mRNA level. [score:5]
In ductal carcinoma samples, CpG islands on the upstream of primary-miR-543 have been shown to be hypermethylated, which directly results in the down-regulation of mature miR-543 [14]. [score:5]
miR-543 overexpression inhibits tumor growth and metastasis of CRC cells in vivo. [score:5]
Two highly metastatic CRC cell lines, SW620 and LoVo, which have very low endogenous miR-543 expression, were stably infected with a lentivirus expressing miR-543 (Supplementary Figure S1). [score:5]
For stable knockdown of miR-543 in HCT116 cells, pLL3.7-puro containing the best hairpin sequence targeting miR-543 (GCGGTGCACTTCTTTTTCA) or a control plasmid (control hairpin) was co -transfected with pMDL, REV and VSVG. [score:4]
Figure 2(A, B) Dual luciferase reporter assay analysis of the effects of miR-543 overexpression on the activities of 3′UTRs of predicted target genes in 293T (A) and SW620 cells (B). [score:4]
Transwell assays showed that overexpressing of miR-543 in SW620 and LoVo cells significantly inhibited cell migration (Figure 4A) and invasion (Figure 4B) in vitro. [score:4]
Moreover, tumors from miR-543 -overexpressing cells had lower Ki67 expression compared with tumors from controls (Figure 5C). [score:4]
KRAS, MTA1 and HMGA2 are direct targets of miR-543. [score:4]
We demonstrated that miR-543 is downregulated in human CRC samples, mouse CRC tissues and CRC cell lines with highly metastatic potential. [score:4]
However, the underlying mechanisms that regulate miR-543 expression remain elusive. [score:4]
Moreover, in agreement with this result, knockdown of endogenous miR-543 increased the mRNA expression of MTA1, HMGA2, STAT3, MMP2, MMP9 and LOX but decreased the level of miR-200b. [score:4]
Western Blot analysis further revealed that miR-543 overexpression decreased the expression of KRAS and Cyclin D1 and the phosphorylation level of MEK (p-MEK) and ERK (p-ERK) compared with controls (Figure 3F). [score:4]
It has been reported that miR-543 is downregulated in breast cancer [14] and endometrial cancer [15] but functions as an oncogene in hepatocellular carcinoma [16]. [score:4]
Figure 7Representative immunohistochemical staining images of the expression of KRAS, MTA1 and HMGA2 in two paired primary CRC tissues with low or high level of miR-543 and analyses of relative average integrated optical density (IOD) using Image Pro-Plus software. [score:3]
Taken together, these data demonstrate that miR-543 expression is reduced in clinical CRC specimens and mouse CRC tissues, and its level is inversely correlated with the metastatic potential of CRC cell lines and the metastatic status of patients with CRC. [score:3]
Similar inhibitory effects of miR-543 on tumor metastasis were observed in the mice bearing LoVo-Ctrl or LoVo-miR-543 cells (Figure 5E; Supplementary Figure S6B). [score:3]
We next isolated xenograft tumors and confirmed that the overexpression of miR-543 in SW620 cells significantly decreased subcutaneous tumor growth compared with the control groups, and the volumes and weights of the tumors of the nude mice injected with miR-543 -overexpressing cells decreased compared with those of the control group (Figure 5A). [score:3]
As a member of a miRNA cluster located in the imprinted DLK1-DIO3 region on human chromosome 14, miR-543 has been reported to function as a tumor suppressor in breast cancer and endometrial cancer [14, 15], whereas it was found to promote the tumorigenesis of hepatocellular carcinoma [16]. [score:3]
Clinical correlation analysis of the level of miR-543 and its targets in CRC tissues. [score:3]
Moreover, the overexpression of miR-543 significantly decreased the colony numbers of SW620 and LoVo cells (Figure 3C and 3D). [score:3]
We found that miR-543 overexpression in CRC cells decreased the mRNA and protein levels of MTA1 and STAT3 and the mRNA level of their downstream genes MMP2 and MMP9 (Figure 4C and 4D). [score:3]
SW620 and LoVo cells that stably overexpress miR-543 or their control cells were infected with a virus encoding the luciferase gene and then subcutaneously injected into nude mice and analyzed after 4 weeks. [score:3]
Moreover, the phosphorylation level of p-FAK, a downstream effector of LOX [27], was also decreased upon miR-543 overexpression (Figure 4D). [score:3]
LoVo-miR-543 cells were transfected with miRNA-resistant expression constructs for KRAS, MTA1 or HMGA2. [score:3]
For the Matrigel-coated membrane Transwell invasion assays, 8 × 10 [4] SW620, 8 × 10 [4] LoVo, 10×10 [4] HCT116 cells or the same number of corresponding miR-543 -overexpressing or miR-543-knockdown cells were seeded in the top chambers of Transwell plates. [score:3]
For migration assays, 3 × 10 [4] SW620, 3 × 10 [4] LoVo, 5 × 10 [4] HCT116 cells or the same number of corresponding miR-543 -overexpressing or miR-543-knockdown cells were seeded in the top chambers. [score:3]
Representative immunohistochemical staining images of the expression of KRAS, MTA1 and HMGA2 in two paired primary CRC tissues with low or high level of miR-543 and analyses of relative average integrated optical density (IOD) using Image Pro-Plus software. [score:3]
To extend our findings to human CRC, we examined whether the miR-543-related suppression of KRAS, MTA1 and HMGA2 in CRC cells is clinically relevant. [score:3]
miR-543 suppresses CRC cell migration and invasion in vitro. [score:3]
First, we cloned 3′UTRs that contain putative miR-543 binding sites into the pmiR report luciferase construct, and each was co -transfected with a miR-543 expression plasmid into HEK293T and SW620 cells. [score:3]
Figure 1(A, B) qRT-PCR analysis of miR-543 expression in human CRC tissues and matched normal colon tissues from 45 patients with CRC. [score:3]
Using in silico analysis and dual-luciferase reporter assays, we identified KRAS, MTA1 and HMGA2 as three new direct miR-543 downstream targets. [score:3]
Clinicopathologic analysis revealed that the expression of miR-543 was also negatively correlated with distant metastasis status (Figure 1C) and N classification (Table 1); however, no significant difference was observed between the level of miR-543 and sex, age or T classification of patients with CRC (Table 1). [score:3]
However, the inhibitory effects were abolished when the putative miR-543 seed -binding regions in the 3′UTRs of KRAS, MTA1 and HMGA2 were mutated (Figure 2C and 2D). [score:3]
As shown in Figure 5D, bioluminescence imaging revealed that miR-543 overexpression significantly reduced the metastasis of SW620 cells in nude mice. [score:3]
miR-543 has been described as a tumor suppressor gene for breast cancer and endometrial cancer [14, 15] but as an oncogene for hepatocellular carcinoma [16]. [score:3]
miR-543 inhibits CRC cell proliferation in vitro. [score:3]
Collectively, these observations demonstrate that miR-543 inhibits the tumor growth and metastasis of CRC cells in vivo. [score:3]
Both our in vitro and in vivo results support that miR-543 significantly inhibits the growth and metastasis of CRC. [score:3]
KRAS, MTA1 and HMGA2 are downstream targets of miR-543. [score:3]
MTA1 and HMGA2 have been reported to promote EMT and the acquisition of metastatic potential for CRC epithelial cells [22, 23]; thus, we next determined whether the suppression of the migration and invasion of CRC cells by miR-543 was an EMT-related behavior. [score:3]
For the generation of stable miR-543 -overexpressing cell lines, a lentivirus -mediated packaging system containing four plasmids—pCDH-miR-543 or control plasmid (scrambled miRNA), pMDL, REV and VSVG—was used. [score:3]
Bioluminescence imaging results showed that mice injected with SW620-Ctrl cells formed larger tumors than those bearing miR-543 -overexpressing CRC cells (Figure 5A). [score:3]
Inverse correlation between miR-543 and its targets in clinical CRC samples. [score:3]
These data indicate that miR-543 inhibits the tumor growth of CRC cells in vivo. [score:3]
Furthermore, the suppression of endogenous miR-543 dramatically promoted the migration (Figure 6E) and invasion (Figure 6F) of HCT116 cells. [score:3]
miR-543 inhibits CRC cell proliferation in vitroTo evaluate the role of miR-543 in CRC progression, we first determined the effects of miR-543 overexpression on the biological functions of human CRC cell lines. [score:3]
We isolated several organs that were reported to have higher CRC metastatic tropism [30] and found that mice bearing miR-543 -overexpressing SW620 cells had less intestinal and liver metastases than control mice (Figure 5D; Supplementary Figure S6A). [score:3]
As shown in Figure 6A and 6B, miR-543 knockdown led to a significant increase in cell proliferation and colony number. [score:2]
Thus, further investigations are needed to determine whether this epigenetic mechanism or other events are causal factors for the downregulation of miR-543 in CRC progression. [score:2]
These in vivo data indicate that knockdown of miR-543 markedly promoted the tumor growth and metastasis of CRC cells. [score:2]
Knockdown of miR-543 promotes the proliferation, invasion and metastasis of CRC cells in vitro and in vivo. [score:2]
Moreover, the metastatic ability of HCT116 cells significantly increased when endogenous miR-543 was knocked down (Figure 6H). [score:2]
Conversely, knockdown of miR-543 promotes the proliferation, invasion and metastasis of CRC cells in vitro and in vivo. [score:2]
HCT116 cells that stably knockdown miR-543 or their control cells were subcutaneously injected into nude mice for 4 weeks and analyzed by bioluminescence imaging. [score:2]
In addition, we also observed that ectopic expression of miR-543 reduced the levels of pro- and cleaved- MMP2 and MMP9 in SW620 and LoVo cells by using gelatin zymography assay (Supplementary Figure S3). [score:2]
We found that miR-543 expression was reduced by nearly 3-fold in the CRC tissues compared with their corresponding nontumorous colorectal tissues (median 5.8 and 15.7, respectively; p < 0.001) (Figure 1B). [score:2]
As shown in Figure 6G, mice injected with HCT116-Ctrl cells formed smaller tumors than those mice bearing miR-543-knockdown CRC cells. [score:2]
Dual-luciferase reporter assays revealed that the luciferase activities of KRAS, MTA1 and HMGA2 but not FMNL2, SIRT1 or ADAM9 significantly decreased in both HEK293T (Figure 2A) and SW620 cells (Figure 2B) upon miR-543 overexpression. [score:2]
Thus, the loss-of-function data demonstrate that miR-543 knockdown promotes the proliferation, migration and invasion of CRC cells in vitro. [score:2]
miR-543 knockdown promotes the proliferation, invasion and metastasis of HCT116 cells in vitro and in vivo. [score:2]
Knockdown of miR-543 promotes the proliferation, invasion and metastasis of CRC cells in vitro and in vivoWe further performed loss-of-function experiments to verify the function of miR-543 in CRC cells. [score:2]
MTT assays revealed that ectopic overexpression of miR-543 in SW620 and LoVo cells resulted in a significant decrease in cell proliferation compared with control cells (Figure 3A and 3B). [score:1]
We next evaluated whether miR-543 could inhibit the ability of CRC cells to metastasize to the intestines and liver. [score:1]
293T or SW620 cells were seeded into a 24-well plate and cotransfected with miR-543 or control and 3′UTR-luciferase plasmids. [score:1]
Correlation of relative miR-543 expression with the clinicopathological characteristics of patients with colorectal cancer. [score:1]
The level of miR-543 was relatively lower in highly metastatic CRC cell lines than those in the four tumorigenic but low-metastatic cell lines (Figure 1D), indicating that miR-543 level is inversely correlated with the metastatic potential of CRC cell lines. [score:1]
Our study suggests that miR-543 may be a critical determinant of CRC progression. [score:1]
Images of isolated tumors (middle) and quantitation of tumor weights (right) from mice 28 days after injection with HCT116-sh-Ctrl or HCT116-sh-miR-543 cells. [score:1]
To investigate the clinicopathological significance of miR-543 in CRC, we first detected the expression of miR-543 in 45 paired human CRC tissues and matched normal colorectal tissues. [score:1]
We further determined the level of miR-543 in highly metastatic human CRC cell lines (SW620 and LoVo) and CRC cell lines with low metastatic potential (HCT116, LS174T, HT29 and Caco-2). [score:1]
Bioluminescence images of intestines and livers isolated from mice 28 days after intrasplenic injection with SW620-Ctrl or SW620-miR-543 cells (middle). [score:1]
Images of isolated tumors (middle) and quantitation of tumor weights (right) from mice 28 days after injection with LoVo-Ctrl or LoVo-miR-543 cells. [score:1]
We further performed loss-of-function experiments to verify the function of miR-543 in CRC cells. [score:1]
These findings demonstrate that miR-543 may function as a tumor suppressor or oncogene in a context -dependent manner; therefore, the discrepancy that miR-543 exhibits opposing effects in different tumors deserves further investigation. [score:1]
Using qRT-PCR analysis, we found that the level of miR-543 in CRC tumors isolated from APC [Min] mice was significantly lower than that in colorectal epithelium tissues from wild-type mice (Figure 1E). [score:1]
Bioluminescence images of intestines and livers isolated from mice 28 days after intrasplenic injection with HCT116-sh-Ctrl or HCT116-sh-miR-543 cells (middle). [score:1]
Bioluminescence images of intestines and livers (left) isolated from mice 28 days after intrasplenic injection with LoVo-Ctrl or LoVo-miR-543 cells (middle). [score:1]
Images of isolated tumors (middle) and quantitation of tumor weights (right) from mice 28 days after injection with SW620-Ctrl or SW620-miR-543 cells. [score:1]
To evaluate the role of miR-543 in CRC progression, we first determined the effects of miR-543 overexpression on the biological functions of human CRC cell lines. [score:1]
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2
[+] score: 32
Inhibitors for miR-7b and miR-28 upregulated CRX expression as expected (Fig.   3A,B), while miR-543 inhibitor did not upregulate CRX (Fig.   3C) and so was excluded from further analysis. [score:13]
When we transfected MGDPs with miR-7b, miR-28, miR-543 mimics and their respective inhibitors (MmiR-AN1287-SN-10, MmiR-AN0622-SN-10, MmiR-AN0362-SN-10, respectively), all three miRNA mimics suppressed CRX expression. [score:7]
When respective miRNA mimics were transiently transfected to MGDPs for 2 days, real-time polymerase chain reaction (PCR) demonstrated that only 3 miRNAs, miR-7b, miR-543, and miR-28, suppressed CRX expression (Table  1). [score:5]
CRX gene expression measured by qPCR in cells transfected with miR-7b, miR-543, or miR-28 mimic (left panels) or corresponding inhibitors (right panels). [score:3]
These searches identified 8 miRNAs (miR-7a, miR-7b, miR-28, miR-186, miR-381, miR-876, miR-543, and miR-708) that might target CRX. [score:3]
control miR-7b mimcs CRX 1.005 ± 0.090.43 ± 0.04 [*] miR-7b 1.00 ± 0.042.62 ± 0.16 [*] Con miR-186 mimics CRX 1.05 ± 0.14 1.07 ± 0.09 miR-186 1.00 ± 0.021.25 ± 0.02 [*] Con miR-7a mimics CRX 1.02 ± 0.08 0.91 ± 0.016 miR-7a 1.01 ± 0.15 1.15 ± 0.06 Con miR-876 mimics CRX 1.00 ± 0.04 1.14 ± 0.05 miR-876 1.00 ± 0.09 1.25 ± 0. 14 Con miR-708 mimics CRX 1.00 ± 0.11 1.02 ± 0.10 miR-708 1.00 ± 0.03 0.89 ± 0.07 Con miR-381 mimics CRX 1.01 ± 0.10 1.25 ± 0.15 miR-381 1.00 ± 0.01 0.83 ± 0.09 Con miR-543 mimics CRX 1.00 ± 0.060.39 ± 0.02 [*] miR-543 1.09 ± 0.142.56 ± 0.18 [*] Con miR-28 mimics CRX 1.00 ± 0.040.36 ± 0.02 [*] miR-28 1.00 ± 0.092.08 ± 0. 10 [*] * P < 0.05. [score:1]
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3
[+] score: 31
Less is known about the cellular targets and function of miR-450b-3p, miR-455*, miR-543 and miR-872 (all downregulated in our studies). [score:6]
Of the ten miRNAs downregulated in Ercc1 [−/−] MEFs, eight (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) were also down-regulated in both the progeroid and old WT mouse livers compared to the WT young (20 week) control mouse livers (Figure 1). [score:6]
MiR-455*, miR-497 and miR-543 were significantly downregulated in P7 Ercc1 [−/−] MEFs compared to P7 WT MEFs (Table 1) and P7 versus P3 Ercc1 [−/−] MEFs (Table 3)grown at 3% O [2], suggesting that these miRNAs may be dysregulated as a result of deficient DNA repair and/or sequential passaging. [score:4]
Eight miRNAs (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) are significantly downregulated in the livers of progeroid Ercc1 [−/Δ] and naturally aged mice compared to young adult mice (Figure 1). [score:3]
Additionally, we demonstrate that several miRNAs differentially expressed in the Ercc1 [−/−] MEFs (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) were also dysregulated in liver tissues of both progeroid Ercc1 [−/Δ] and old WT mice compared to young WT mice. [score:3]
Additionally, we identified six downregulated miRNAs (miR-301a, miR-326, miR-455*, miR-497, miR-543 and miR-872) in late-passage P7 Ercc1 [−/−] MEFs compared to the WT MEFs grown in 3% O [2] (Table 1). [score:3]
Previously confirmed gene targets of the miRNAs identified in this study that are linked to cellular senescence and aging (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b) are listed in Supplemental Table S1. [score:3]
In summary, we identified several miRNAs that are similarly dysregulated in senescent primary MEFs and senescent tissues of progeroid and naturally aged mice (miR-449a, miR-455*, miR-128, miR-497, miR-543, miR-450b-3p, miR-872 and miR-10b). [score:2]
We analyzed the levels of 13 miRNAs confirmed to be dysregulated in P7 Ercc1 [−/−] MEFs compared to P3 Ercc1 [−/−] MEFs (miR-680, miR-320, miR-22, miR-449a, miR-455*, miR-675-3p, miR-128, miR-497, miR-543, miR-450b-3p, miR-872, miR-369-5p and miR-10b) in RNA samples prepared from the livers of WT young (20 weeks), the progeroid Ercc1 [−/Δ] mice, and WT old mice (30 months). [score:1]
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4
[+] score: 23
The current data suggest that multiple miRNAs, including miR-9, miR-137, miR-155, miR-301a, miR455, and miR-543 (Figure 7A and Figure 8A), regulate c-Maf expression through its 3′-UTR. [score:4]
We conclude that miR-9, miR-137, miR-200c, miR-381, miR-455, miR-495, and miR-543 represent an FGF2 -dependent system of multiple miRNAs that target specific genes operating in pathways and processes related to the lens differentiation (via c-Maf, Med1/PBP, N-myc, and Nfat5), miRNA-regulated RNA processing (via Cpsf6 and Tnrc6b) and nuclear/chromatin -based processes (via Med1/PBP, As1l, and Kdm5b/Jarid1b/Plu1). [score:4]
We found that seven miRNAs, including miR-9, miR-137, miR-200c, miR-381, miR-455, miR-495, and miR-543, target at least two “early” genes examined (i. e., c-Maf, N-Myc, and Nfib). [score:3]
Three miRNAs from this cluster, including miR-495, miR-543, and miR-381, represent a group of most highly connected miRNAs in this system (Figure 6A) and regulate together multiple genes known to regulate lens fiber cell differentiation, including c-Maf (Figure 7 and Figure 10). [score:3]
This gross analysis is consistent with our findings of genes regulated by miR-495, miR-543, and miR-381 in lens that belong to these similar categories (Figure 5). [score:2]
We predict that several important regulatory genes of lens fiber cell differentiation, including c-Maf, Kdm5b/Jarid1b, Med1/PBP, Nfat5/OREBP, and N-Myc, are connected by multiple shared miRNAs, with four of them, including miR-381, miR-495, miR-382, and miR-543, encoded by a miRNA cluster on rat chromosome 6, a syntenic region with mouse chromosome 12, and human 14q32.2 imprinted regions. [score:2]
The miR-495 and miR-543 are neighbors, and miR-381 is located ~12.7 kb from miR-495. [score:1]
Seven miRNAs, including miR-9, miR-137, miR-200c, miR-381, miR-455, miR-495, and miR-543, and connections to specific functional groups of genes are shown. [score:1]
The miR-381, miR-495, miR-543, and miR-382 form a miRNA-gene cluster on rat chromosome 6q32. [score:1]
The most connected miRNA identified here through the 12 top-ranking transcripts, including miR-495, miR-200c, miR-543, miR-381, and miR-9 (Figure 6A), retained their high-connectivity positions as identified by independent analysis shown earlier in Figure 6A. [score:1]
Notably, miR-381, miR-495, and miR-543 form a miRNA-gene cluster on rat chromosome 6, and its syntenic regions on mouse and human chromosome 12 and 14, respectively (Sewer et al. 2005). [score:1]
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5
[+] score: 15
MiRNA target site/Species Human Mouse Cow Dog Chicken FrogTargeting Twist2 miR-15b-3p + − + + − − − miR-33-5p + + + + − + − miR-137-3p + + + + − + − miR-145a-5p + + + + − − + miR-151-5p + + + + − + − miR-214-5p + + + + − − − miR-326-3p + + + + − − − miR-337-3p + + + + − + − miR-361-5p + + + + − − − miR-378a-5p + + + + − − − miR-381-3p + + + + − + − miR-409-3p + + + + − − − miR-450b-5p + + + + − + − miR-508-3p + + + + − − − miR-543-3p + + + + − − − miR-576-5p + + + + − − − miR-580 + + + + − − − miR-591 + + + + − − − MicroRNAs underlined were tested in this study. [score:5]
The following miRNAs were tested for their potential to repress Twist1 translation in the human lung carcinoma cell line H1299: miR-33, miR-145a, miR-151, miR-326, miR-337, miR-361, miR-378a, miR-381, miR-409 and miR-543 (Fig. 1). [score:3]
While two of them, miR-539 and miR-300 have no target site in the murine Twist1 3′UTR, a third, miR-543 did not show a significant effect in our screen. [score:3]
While this work was under revision, miR-214 [36], miR-300, miR-539 and miR-543 [37] have also been reported to target the TWIST1 3′UTR. [score:3]
The miRBase accession numbers for miRNAs are: mmu-miR-33 (MI0000707), mmu-miR-145a (MI0000169), mmu-miR-151 (MI0000173), mmu-miR-326 (MI0000598), mmu-miR-337 (MI0000615), mmu-miR-361 (MI0000761), mmu-miR-378a (MI0000795), mmu-miR-381 (MI0000798), mmu-miR-409 (MI0001160) and mmu-miR-543 (MI0003519). [score:1]
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[+] score: 12
Other miRNAs from this paper: mmu-mir-486a, mmu-mir-486b
In general, miR-543 was upregulated and miR-486-5p was downregulated in the HCC cells compared to the LO2 cells (Figure 5C & Supplementary Figure 1). [score:6]
Therefore, we analyzed mRNA target-predicting algorithms, miRanda and miRDB to identify potential miRNAs that bind to 3′ UTR of NEK2 and identified miR-543 and miR-486-5p as possible candidates (Figure 5A, 5B). [score:3]
Next, we analyzed the expression levels of miR-543 and miR-486-5p in normal liver cell LO2 and HCC cell lines, namely, SMMC-7721, Hep3B and HepG2 by qRT-PCR. [score:3]
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[+] score: 9
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-24-1, hsa-mir-24-2, hsa-mir-25, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-134, mmu-mir-137, mmu-mir-138-2, mmu-mir-145a, mmu-mir-24-1, hsa-mir-192, mmu-mir-194-1, mmu-mir-200b, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-215, hsa-mir-221, hsa-mir-200b, mmu-mir-296, mmu-let-7d, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-137, hsa-mir-138-2, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-134, hsa-mir-138-1, hsa-mir-194-1, mmu-mir-192, 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-24-2, mmu-mir-346, hsa-mir-200c, mmu-mir-17, mmu-mir-25, mmu-mir-200c, mmu-mir-221, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-200a, hsa-mir-296, hsa-mir-369, hsa-mir-346, mmu-mir-215, gga-let-7i, gga-let-7a-3, gga-let-7b, gga-let-7c, gga-mir-221, gga-mir-17, gga-mir-138-1, gga-mir-124a, gga-mir-194, gga-mir-215, gga-mir-137, gga-mir-7-2, gga-mir-138-2, gga-let-7g, gga-let-7d, gga-let-7f, gga-let-7a-1, gga-mir-200a, gga-mir-200b, gga-mir-124b, gga-let-7a-2, gga-let-7j, gga-let-7k, gga-mir-7-3, gga-mir-7-1, gga-mir-24, gga-mir-7b, gga-mir-9-2, dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-192, dre-mir-221, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, 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-7a-3, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-17a-1, dre-mir-17a-2, dre-mir-24-4, dre-mir-24-2, dre-mir-24-3, dre-mir-24-1, dre-mir-25, dre-mir-92b, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-137-1, dre-mir-137-2, dre-mir-138-1, dre-mir-145, dre-mir-194a, dre-mir-194b, dre-mir-200a, dre-mir-200b, dre-mir-200c, dre-mir-430c-2, dre-mir-430c-3, dre-mir-430c-4, dre-mir-430c-5, dre-mir-430c-6, dre-mir-430c-7, dre-mir-430c-8, dre-mir-430c-9, dre-mir-430c-10, dre-mir-430c-11, dre-mir-430c-12, dre-mir-430c-13, dre-mir-430c-14, dre-mir-430c-15, dre-mir-430c-16, dre-mir-430c-17, dre-mir-430c-18, dre-mir-430a-2, dre-mir-430a-3, dre-mir-430a-4, dre-mir-430a-5, dre-mir-430a-6, dre-mir-430a-7, dre-mir-430a-8, dre-mir-430a-9, dre-mir-430a-10, dre-mir-430a-11, dre-mir-430a-12, dre-mir-430a-13, dre-mir-430a-14, dre-mir-430a-15, dre-mir-430a-16, dre-mir-430a-17, dre-mir-430a-18, dre-mir-430i-1, dre-mir-430i-2, dre-mir-430i-3, dre-mir-430b-2, dre-mir-430b-3, dre-mir-430b-4, dre-mir-430b-6, dre-mir-430b-7, dre-mir-430b-8, dre-mir-430b-9, dre-mir-430b-10, dre-mir-430b-11, dre-mir-430b-12, dre-mir-430b-13, dre-mir-430b-14, dre-mir-430b-15, dre-mir-430b-16, dre-mir-430b-17, dre-mir-430b-18, dre-mir-430b-5, dre-mir-430b-19, dre-mir-430b-20, mmu-mir-470, hsa-mir-485, hsa-mir-496, dre-let-7j, mmu-mir-485, mmu-mir-369, hsa-mir-92b, gga-mir-9-1, hsa-mir-671, mmu-mir-671, mmu-mir-496a, mmu-mir-92b, hsa-mir-543, gga-mir-124a-2, mmu-mir-145b, mmu-let-7j, mmu-mir-496b, mmu-let-7k, gga-mir-124c, gga-mir-9-3, gga-mir-145, dre-mir-138-2, dre-mir-24b, gga-mir-9-4, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3, gga-mir-9b-1, gga-let-7l-1, gga-let-7l-2, gga-mir-9b-2
In this scenario, in vivo overexpression of miR-369-3p, miR-496 and miR-543 in radial glial cells (RGCs) which can differentiate into neurons, negatively regulate N-cadherin (Ncad) and lower levels of Ncad conduce to their premature neuronal differentiation which is prevented by expressing a miRNA-resistant Ncad version (Rago et al., 2014). [score:6]
On the other hand, when miR-369-3p, miR-496 and miR-543 are suppressed, an increase in cell proliferation is observed, which correlates with a decrease in neuronal differentiation (Rago et al., 2014). [score:3]
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[+] score: 5
Some examples include cell stress and damage markers (NKG2-D, DNAJ B), extracellular matrix -regulating genes (serine protease inhibitor A3F), and miRNAs (mir543) (Figures 5A–D). [score:4]
Micro RNA 543 (mir543) has been associated with mesenchymal stem cell differentiation, and thus may be related to changes in the cellular differentiation pathways (Xu et al., 2017). [score:1]
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[+] score: 5
We randomly picked 9 miRNAs (miR-337, miR-540-3p, miR-127, miR-434-5p, miR-329, miR-543-3p, miR-376a, miR-300, and miR-381) expressed from the Dlk1-Dio3 locus and validated their expression by qRT-PCR. [score:5]
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[+] score: 4
FAK has been verified as the target gene for several other miRs (miR-543 and miR-7) in cancer development [17, 31]. [score:4]
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[+] score: 4
As found for 10-87 HP cells and 10-87 T cells, SF-VERO cells and A4497 VERO cells expressed increased levels of miR-376a, miR-654-3p, miR-543, and miR-382 over the levels found in pAGMK cells (Table 4). [score:3]
qRT-PCR analysis confirmed that miR-376a, miR-654-3p, miR-543, miR-382, miR-31, miR-200c, miR-218, and miR-183 paralleled the microarray miRNA levels. [score:1]
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[+] score: 3
Nrf2 (+/+) Saline—Nrf2(–/–) Saline miR-128, miR-7a, miR-669c, miR-298, miR-543, miR-770-5p, miR-669b* and miR-544-5p S1 Changes in miRNA expression profile after exposure to paraquat. [score:3]
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[+] score: 3
miR-369-3p and two of the seven miRNAs recognized as affecting MET by Haga and Phinney [53], miR-543-3p and miR-494-3p, were in pool one of the miRNA mimics, whose overexpression resulted in a decrease in both AP+ and Oct4-GFP+ cells (Figure 6). [score:3]
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14
[+] score: 3
Finally, the authors identified three microRNAs (miR-134, miR-543, and miR-653) as Braf-rs1 and Braf -targeting and, by mutagenizing their MREs on Braf mRNA, proved that they are the mediators of the protective effects exerted by the pseudogene on the parental gene. [score:3]
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[+] score: 1
These 15 microRNAs include Mir128 (in both -1 and -2 forms) that has been implicated in regulating motor behavior by modulating neuronal signaling networks and excitability in adult neurons [30]; Mir218, Mir369 and Mir543. [score:1]
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