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105 publications mentioning mmu-mir-205 (showing top 100)

Open access articles that are associated with the species Mus musculus and mention the gene name mir-205. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 319
To verify whether miR-205 is capable of regulating FGF2 and VEGFA expression via the binding sites in their 3′-UTRs (Figure 3a), each 3′-UTR containing the predicted miR-205 binding site was cloned downstream of the firefly luciferase coding region in the pMirTarget luciferase vector, resulting in pMirTarget-VEGFA and pMirTarget-FGF2, respectively. [score:10]
Thus overexpression of miR-205 in drug-resistant cells promotes apoptosis by upregulation of Bax and downregulation of survivin and the AKT pathway. [score:9]
Moreover, the addition of VEGFA/FGF2 partially restored PI3K activity and survivin expression, which were abolished by miR-205 overexpression, and also decreased Bax expression, which was induced by miR-205 overexpression (Figure 4c). [score:9]
We transiently transfected cells overexpressing miR-205 with pMirTarget-VEGFA or pMirTarget-FGF2, together with a Renilla luciferase expressing plasmid to normalize for transfection efficiency. [score:9]
In addition, experimental expression of miR-205 in drug-resistant cells led to a downregulation of both VEGFA and FGF2 (Figure 3c), confirming the negative correlation between miR-205 and VEGFA/FGF2 expression. [score:8]
miR-205 directly targets VEGFA and FGF2 and negatively regulates their expression. [score:7]
Furthermore, consistent with in vitro analyses, tumors generated from miR-205 -overexpressed cells had higher expression of Bax, as well as lower expression of survivin, than those generated with control cells (Figure 6f). [score:7]
[49] miR-205 also enhances cisplatin toxicity in castration-resistant prostate cancer cells by targeting RAB27A and LAMP3, [50] whereas in lung cancer, miR-205 overexpression is associated with carboplatin insensitivity by altering the expression of apoptosis-related genes. [score:7]
miR-205 upregulation inhibits tumor growth and enhances breast cancer chemosensitivity to doxorubicin and taxol in vivoThe regulatory role of miR-205 on drug sensitivity was further explored using a mouse xenograft mo del. [score:7]
To further verify whether the phenotype observed after miR-205 overexpression was due to downregulation of VEGFA and FGF2, a rescue methodology was adopted. [score:6]
44, 45 miR-205 is upregulated in the progenitor subpopulation of a mouse mammary epithelial cell line, thus promoting cell proliferation and tumor initiation through targeting PTEN. [score:6]
As miR-205 is downregulated in drug-resistant breast cancer cell lines, we hypothesized that, if it would contribute to the drug-resistant phenotype, its ectopic expression might restore drug sensitivity. [score:6]
[46] However, increasing evidence shows downregulation of miR-205 in metastatic breast cancer cell lines, triple -negative breast cancer and metastatic breast secondary tumors, suggesting a tumor-suppressor role by reducing cellular proliferation, tumor angiogenesis and metastasis. [score:6]
miR-205 upregulation inhibits tumor growth and enhances breast cancer chemosensitivity to doxorubicin and taxol in vivo. [score:6]
MiR-205 expression was upregulated 24-fold in MCF-7/A02-miR-205 cells and 32-fold in CALDOX-miR-205 cells (Figure 2a). [score:6]
In addition, an approximately 35% reduction in luciferase expression was also observed in both MCF-7/A02-mir-205 versus MCF-7/A02-NC and CALDOX-mir-205 versus CALDOX-NC when transfected with pMirTarget-FGF2. [score:5]
Indeed, an approximately 40% reduction in luciferase expression was observed in both MCF-7/A02-mir-205 versus MCF-7/A02-NC and CALDOX-mir-205 versus CALDOX-NC when transfected with pMirTarget-VEGFA. [score:5]
RT-qPCR and western blotting results revealed that overexpressing miR-205 repressed survivin and promoted Bax expression in drug-resistant cells (Figures 2g and h). [score:5]
Here, using chemoresistant breast cancer cell mo dels, we show that miR-205 targets VEGFA as well as FGF2 mRNA 3′-UTR and represses their expression, leading to impaired PI3K/AKT signaling and increased apoptosis both in vitro and in vivo. [score:5]
Although we have ruled out ZEB-1 as the target gene of miR-205 in these two drug-resistant cell lines in vitro, it is unexpected that miR-205 overexpression in CALDOX cells leads to the failure of engraftment in vivo. [score:5]
To confirm the negative correlation between the decreased VEGFA/FGF2 and enhanced miR-205 observed in breast cancer cell lines, we further analyzed the expression of VEGFA/FGF2 by quantitative PCR in the 30 patient samples that show positive correlation between miR-205 expression and response to TAC (Figure 1a). [score:5]
In prostate cancer, reduced expression of E-cadherin leads to docetaxel insensitivity, which is partially mediated by reduced miR-205 expression. [score:5]
As binding to target sequences is not very stringent, miRNAs have a plethora of potential targets and it is plausible that additional molecules, other than VEGFA and FGF2, may be involved in mediating miR-205 chemo-sensitizing effect. [score:5]
We hypothesized that luciferase expression would decrease in cells overexpressing miR-205 when transfected with the reporter plasmid incorporating VEGFA 3′-UTR or FGF2 3′-UTR but not in the control. [score:5]
Equally, miR-205 -overexpressing cells were more sensitive to taxol, and the IC [50] values of miR-205 -overexpressing cells decreased between 56 and 84% (84.2% in MCF-7/A02-miR-205 cells and 56.8% in CALDOX-miR-205 cells; Figure 2b and Supplementary Figure S1). [score:5]
Thus suppression of PI3K/AKT activity mimics the chemoresistant phenotype obtained by miR-205 overexpression. [score:5]
miR-205 is downregulated in drug-resistant breast cancer cells. [score:4]
In addition, miR-205 -mediated chemosensitivity is, at least in part, mediated by downregulation of VEGFA, FGF2 and subsequent increase of cell apoptosis. [score:4]
Thus the chemo-sensitizing effect of miR-205 in breast cancer depends on VEGFA/FGF2 downregulation. [score:4]
We found miR-205 downregulated in both MCF-7/A02 and CALDOX cells by approximately 90 and 75%, respectively (Figure 1b). [score:4]
Thus miR-205 is downregulated in multidrug-resistant cell lines. [score:4]
32, 33 However, we did not observe any regulation of ZEB-1 upon expression of miR-205 in either drug-resistant MCF-7/A02 or CALDOX cells (Supplementary Figures S2A and B). [score:4]
Therefore, our study reveals a novel mechanism for miR-205 as a tumor suppressor and regulator of chemotherapy response. [score:4]
Overexpression of miR-205 restores drug sensitivity by promoting apoptosis in breast cancer cells. [score:3]
In this study, we show that miR-205 expression levels might be useful for predicting response to TAC regimen as NAC treatment in breast cancer patients. [score:3]
32, 34, 47, 48 In addition, miR-205 has been found to modulate chemosensitivity in several human cancers but has opposite roles through targeting different genes. [score:3]
[26] indicated that in both drug-resistant cells ectopic expression of miR-205 increased the percentage of cells undergoing apoptosis after taxol treatment (Figure 2d). [score:3]
Thus overexpression of miR-205 restores sensitivity to doxorubicin and taxol in drug-resistant breast cancer cells. [score:3]
Thus miR-205 expression correlates with NAC response. [score:3]
[28] Consistent with the increased apoptosis in the taxol -treated miR-205 -overexpressing cells, we observed a marked increase in the levels of cleavage of caspase-3 and PARP in CALDOX-miR-205 cells, especially after taxol treatment (Figure 2f). [score:3]
Altogether, these data strongly support a tumor-suppressor role and promoter of chemosensitivity for miR-205 by repression of VEGFA and FGF2 and enhancing cell apoptosis in breast cancer. [score:3]
In conclusion, our data demonstrate that elevated miR-205 expression levels enhance sensitivity to TAC chemotherapy in breast cancer patients. [score:3]
We found that both the expression of VEGFA and FGF2 showed a negative correlation with miR-205 levels in these 30 patients (rs=−0.4851, P=0.0078 for VEGFA and miR-205, rs=−0.38, P=0.0349 for FGF2 and miR-205; Figure 3e). [score:3]
This suggests that miR-205 may also be suppressing breast cancer cells' proliferation or tumorigenesis via additional mechanisms in line with our data (Figure 2c and Supplementary Figure S1B) and those found in melanoma [52] and osteosarcoma. [score:3]
As caspases are key mediators of apoptosis, [27] we analyzed the activation of both initiator and effector caspases in miR-205 -overexpressing cells in response to taxol treatment. [score:3]
It is also noteworthy that miR-205 overexpression increased caspase activity in both drug-free cell lines, although the activation due to drug treatment was much higher (Figure 2e). [score:3]
Bioinformatic analysis indicates that both VEGFA and FGF2 are potential targets for miR-205 (Figure 3a), and this has been confirmed for VEGFA in osteosarcoma [24], thyroid cancer [25] and breast cancer MDA-MB-231 cells. [score:3]
Thus miR-205 binds VEGFA and FGF2 mRNA 3′-UTRs and decreases their expression in breast cancer cells. [score:3]
High miR-205 expression in breast cancer tissues strongly associates with increased sensitivity to TAC regimen, which is corroborated by other reports indicating an association between high miR-205 levels and better distant relapse-free survival in breast cancer patients. [score:3]
miR-205 expression levels correlate with NAC response in breast cancer patients. [score:3]
[61] Here we present data indicating that miR-205 targets VEGFA and FGF2 in breast cancer cells leading to decreased activity of PI3K/AKT signaling pathway, increased apoptosis and restoration of drug sensitivity in drug-resistant breast cancer cells. [score:3]
To test this hypothesis, we generated stable MCF-7/A02 and CALDOX cells overexpressing miR-205 by lentiviral transfection (MCF-7/A02-miR-205 and CALDOX-miR-205, respectively). [score:3]
Remarkably, tumors generated with CALDOX cells overexpressing miR-205 failed to engraft, despite the fact that the controls reached approximately 300 mm [3] 4 weeks postimplantation (Figures 6d and e). [score:3]
Thus the lack of correlation between ZEB-1 and miR-205 expression levels suggests that the restoration of chemosensitivity by miR-205 in MCF-7/A02 and CALDOX cells is ZEB-1 independent. [score:3]
Collectively, these data suggest that the loss of miR-205 induces VEGFA/FGF2 expression, thus conferring chemoresistance in breast cancer. [score:3]
Similar to miR-205 overexpression, blocking PI3K/AKT signaling was accompanied by a resensitization of drug-resistant MCF-7/A02 and CALDOX cells to taxol, with an increment of apoptotic levels by 20% (Figure 4d). [score:3]
The addition of either VEGFA or FGF2 significantly increased the doxorubicin IC [50] values of miR-205 -overexpressing cells between 2.31- and 4.24-fold (Figure 4a). [score:3]
MCF-7/A02 and CALDOX cells were infected with vector control (NC) or miR-205-overexpression virus and selected with puromycin as previously described. [score:3]
miR-205 overexpression promotes cell apoptosis, induces caspase activity and modulates apoptosis-related proteins. [score:3]
To confirm the positive correlation between miR-205 and TAC response shown in breast cancer patients, we further analyzed its expression in two pairs of chemosensitive and chemoresistant breast cancer cell lines. [score:3]
In agreement with the raised IC [50] values, lowered caspase-3/7 and caspase-9 activities were observed in both miR-205 -overexpressing drug-resistant cells in the presence of VEGFA/FGF2 after taxol treatment (Figure 4b). [score:3]
30, 31 We also observed that the induction of cell apoptosis by miR-205 overexpression in both drug-resistant cells was associated with a significant reduction in AKT phosphorylation, suggesting a decrease in PI3K activity (Figure 2h). [score:3]
miR-205 -overexpressing tumors also showed lower human VEGFA and FGF2 mRNA levels, and this was further confirmed at the protein level when human VEGFA and FGF2 plasma concentrations were determined (Figure 6g). [score:3]
miR-205 has recently been reported to increase radiosensitivity and enhance EMT via targeting ZEB1 in breast cancer SUM159, MCF-7 and MDA-MB-231 cell lines. [score:3]
Equally, miR-205 -overexpressing cells were more resistant to taxol in the presence of VEGFA/FGF2, the IC [50] values increasing between 1.49- and 2.12-fold (Figure 4a and Supplementary Figure S3A). [score:3]
In the MCF-7 group, tumors overexpressing miR-205 reached approximately 300 mm [3] at day 45 postimplantation, whereas tumors increased to approximately 1250 mm [3] in the control group (Figures 6a–c). [score:3]
42, 43 miR-205 is located in chromosome 1q32.2 and its expression pattern mirrors that of the miR-200 family. [score:3]
Both caspase 9 and caspase 3/7 activities increased between 2- and 4.5-fold after taxol treatment in drug-resistant cells overexpressing miR-205 when compared with the control cells (Figure 2e). [score:2]
The regulatory role of miR-205 on drug sensitivity was further explored using a mouse xenograft mo del. [score:2]
Drug sensitivity assays indicated that the doxorubicin IC [50] values of miR-205 overexpressing cells decreased between 74 and 82% (74.4% in MCF-7/A02-miR-205 cells and 81.9% in CALDOX-miR-205 cells). [score:2]
To further confirm that PI3K activity is involved in the miR-205/VEGFA and FGF2 axis to regulate chemosensitivity of breast cancer cells, MCF-7/A02 and CALDOX cells were treated with LY294002, a well-characterized selective PI3K/AKT inhibitor. [score:2]
Similar results were also observed in other pairs of sensitive/resistant cancer cell lines such as those derived from K562, MTMEC, HL60 and BJAB cells 17, 21, 22 (Figure 1c), although only breast cancer drug-resistant MTMECs showed similar diminished miR-205 levels as those found in the other breast cancer cell lines (Figure 1b). [score:1]
Chemotherapeutic treatment using a combination of doxorubicin and taxol in the MCF-7/A02-miR-NC and MCF-7/A02-miR-205 mouse groups started at day 15 and was repeated every 3 days. [score:1]
Spearman rank test was used to identify the correlation between miR-205/VEGFA/FGF2 and NAC response rate, as well as the correlation between miR-205 and VEGFA/FGF2. [score:1]
For this, MCF-7/A02-miR-NC, MCF-7/A02-miR-205, CALDOX-miR-NC and CALDOX-miR-205 cells were injected into the mammary fat pad of nude mice. [score:1]
[51] However, the effect of miR-205 in breast cancer chemoresistance is still poorly understood. [score:1]
Moreover, to evaluate the efficacy of miR-205 overexpression on drug resistance, defined as proliferation in the presence of toxic drug concentrations, we stained cell cultures with crystal violet, as a surrogate for cell mass, [23] after 1 week treatment (drug concentrations and time points were determined empirically in a series of preliminary experiments). [score:1]
Our studies provide the rationale for using miR-205 as predictive biomarker to stratify patients before receiving TAC regimen as NAC and developing miR-205 -based therapeutic agents for breast cancer treatment. [score:1]
We performed a linear regression and Spearman rank test and obtained a positive correlation between miR-205 expression, detected by reverse transcription quantitative real-time PCR (qRT-PCR) and NAC response rate, calculated by the alterations in greatest tumor diameter (rs=0.4305, P=0.0175) (Figure 1a). [score:1]
[25] Moreover, miR-205 impaired proliferation to a much higher extent in the presence of doxorubicin or taxol (reduction between 75 and 91% Figure 2c). [score:1]
For this, MCF-7/A02-miR-205 and CALDOX-miR-205 cells were treated with doxorubicin or taxol in the presence or absence of VEGFA/FGF2. [score:1]
Approximately 20% of MCF-7/A02-miR-205 cells were in the early stages of apoptosis (positive annexin V and negative propidium iodide), whereas approximately 18% of CALDOX-miR-205 cells were already in the late stage of apoptosis (positive for both annexin V and propidium iodide) after 48-h taxol treatment (Figure 2d). [score:1]
The efficacy of miR-205 in sensitizing breast cancer to chemotherapy may also support its application as a potential chemo-sensitizing agent. [score:1]
Next we asked whether the drug sensitivity rescue by miR-205 on chemoresistant breast cancer cells was mediated by promoting cell apoptosis. [score:1]
Repression of VEGFA and FGF2 in drug-resistant cells is essential for miR-205 -induced restoration of chemosensitivity. [score:1]
Lentivirus particles carrying miR-205 cloned into pGLV2-U6-Puro and packaging plasmid mix were purchased from GenePharma (Shanghai, China). [score:1]
In order to investigate the correlation of miR-205 expression with NAC response, we collected 30 breast cancer tissue samples from patients before receiving TAC (Table 1), an anthracycline and taxane -based regimen wi dely used as neoadjuvant treatment of breast cancer. [score:1]
As expected, the tumor continued to grow in the MCF-7/A02-miR-NC group, whereas the chemotherapeutic treatment was much more effective in tumors derived from MCF-7/A02-miR-205 cells (Figures 6a and b). [score:1]
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2
[+] score: 248
Using stable transfection with miRNA precursors or inhibitors, we generated (see ) miR-205 -expressing and miR-373 -expressing Caco-2 [WT] clones (Caco-2 [WT]/miR-205; Caco-2 [WT]/miR-373) as well as miR-205-inhibiting and miR-373-inhibiting Caco-2 [D299G] clones (Caco-2 [D299G]/α-miR-205; Caco-2 [D299G]/α-miR-373). [score:11]
We chose stable transfection to overexpress the precursors or inhibitors of miR-205/miR-373 in Caco-2 [WT] or Caco-2 [D299G], because only this approach allowed long-term study of miRNA -mediated induction or inhibition of individual phenotypic effects and permanent gene target modulation. [score:9]
Furthermore, we detected (Fig 4A and 4B) that KLF4 was constitutively increased on mRNA and protein levels in IEC expressing miR-205 (Caco-2 [WT]/miR-205; Caco-2 [D299G]/α-miR-c), which correlated with upregulated expression of MUC2 and TGFβ1 as well as activation of several cell cycle regulators (RB, CDC2, and CCND2). [score:9]
This result resembled the pattern seen in Caco-2 [D299G]/α-miR-c. Reversely, stable inhibition of miR-205 in Caco-2 [D299G] restored protein expression of PKCε, which correlated with suppressed AKT activity. [score:7]
Overexpression of the miR-205- and miR-373- inhibitors led to decreased expression of mature miR-205 and miR-373 in Caco-2 [D299G]. [score:7]
Finally, miR-205 and miR-373 may target (directly or indirectly) many more genes and affect expression of numerous other proteins than identified in this study. [score:7]
The opposite expression pattern was observed when miR-205 expression was basally low (Caco-2 [WT]/miR-c) or ectopically inhibited (Caco-2 [D299G]/α-miR-205). [score:7]
Clones of eGFP-tagged miExpress [™] precursor miRNAs of miR-205 (cat# HmiR0026-MR04) and miR-373 (cat# HmiR0347-MR04) and corresponding precursor miRNA scrambled control clone (miR-c) for vector pEZX-MR04 (cat# CmiR0001-MR04) as well as clones of mCherry-tagged miArrest [™] miRNA inhibitors of miR-205 (α-miR-205; cat# HmiR-AN1314-AM02), miR-373 (α-miR-373; cat# HmiR-AN0461-AM02) and corresponding miRNA inhibitor scrambled control clone (α-miR-c) for vector pEZX-AM02 (cat# CmiR-AN0001-AM02) were obtained from GeneCopoeia (Rockville, USA). [score:7]
Using realtime qPCR, we found (Fig 1C) that Caco-2 [WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in Caco-2 [D299G]. [score:6]
Here, we show that expression levels of miR-205 and miR-373 are specifically upregulated only in mucinous CRC. [score:6]
Expression of miR-205 and miR-373 is upregulated in colon carcinoma cells in-vitroNext, we aimed to determine the effects of miR-205 and miR-373 on cellular biology and function in normal and neoplastic intestinal epithelium in-vitro. [score:6]
Expression of miR-205 and miR-373 is upregulated in colon carcinoma cells in-vitro. [score:6]
The overexpressed pre-miR-205 and pre-miR-373 were successfully processed to increase expression of mature miR-205 and miR-373 in Caco-2 [WT], respectively, as confirmed by qPCR analysis (Fig 1D). [score:5]
Finally, overexpression of miR-205 enhanced chemoresistance of Caco-2 [WT] to MTX, while inhibition of miR-205 promoted chemosensitivity of Caco-2 [D299G] (Fig 6D). [score:5]
0156871.g001 Fig 1Expression levels of (A) miR-205 and (B) miR-373 are significantly upregulated in human mucinous (n = 20) and chronic UC (n = 13) CRC tumor areas compared to matched R [0] margins, as determined by qPCR. [score:5]
Importantly, using the reverse approach, we demonstrate that inhibition of miR-205 in colon carcinoma-like Caco-2 [D299G] suppressed in part these signaling events and and promoted sensitivity to chemotherapy. [score:5]
Expression levels of (A) miR-205 and (B) miR-373 are significantly upregulated in human mucinous (n = 20) and chronic UC (n = 13) CRC tumor areas compared to matched R [0] margins, as determined by qPCR. [score:5]
Overexpression of miR-205 in Caco-2 [WT] mediated derangement of the actin -based cytoskeleton and decreased the expression of ZO-1 in the cell membrane, but did not alter mitotic figures. [score:5]
Overexpression of miR-205 induces increased mucin production, while overexpression of miR-373 causes dedifferentiation. [score:5]
Second, to gain insight into the functional effects of miR-205/miR-373 signaling, as a proof-of-principle, we used a colon cancer cell-culture mo del based on the IEC line Caco-2 which reflected the endogenous miR-205/miR-373 expression pattern in correlation with human disease in patients with MAC. [score:5]
As shown in Fig 6A, Caco-2 [WT]/miR-373 showed loose patches of fibroblast-like, spindle-shaped mesenchymal cells after brief trypsinization, comparable to Caco-2 [D299G]/α-miR-c. In contrast, Caco-2 [D299G]/α-miR-373 maintained adhesive cobblestone-like epithelial morphology after treatment with trypsin, comparable to Caco-2 [WT]/miR-c. No changes in cell adhesion were evident by overexpression or inhibition of miR-205 in Caco-2 [WT] or Caco-2 [D299G], when compared to control clones. [score:4]
Further studies will need to identify the mechanisms that directly control expression of miR-205 and miR-373 during mucinous carcinogenesis in the colon. [score:4]
Overexpression of miR-205 drives goblet cell expansion and modulates cell cycle regulation. [score:4]
miR-205 caused upregulation of two central mediators of intestinal goblet cell expansion, KLF4 and TGFβ1. [score:4]
miR-205 induces expression of distinct molecules related to goblet cell differentiation and cell cycle regulation, as assessed by (A) western blot, (B) qRT-PCR and (C) IPA analysis. [score:4]
In contrast, miR-205/miR-373 expression levels were not elevated in sporadic AC, implying the presence of this specific miRNA signature only in mucin -associated subentities of CRC. [score:3]
miR-205 signaling has recently been implicated to target PKCε [41] and maintain a high phospho-AKT level [26]. [score:3]
First, we showed that the expression patterns of miR-205 and miR-373 differed between human mucinous vs. [score:3]
0156871.g003 Fig 3Expression of miR-205 and miR-373 differentially (A) alters actin cytoskeletal architecture, influences (B) ZO-1 and (C) phospho-β-CATENIN -associated barrier integrity, and (D) induces formation of multinucleated cells with multipolar spindles. [score:3]
Remarkably, Caco-2 [D299G] /α-miR-373 showed normal mitotic metaphases, comparable to Caco-2 [WT]/miR-c. However, inhibition of miR-205 in Caco-2 [D299G] did not change the fibroblast-like appearance with actin cytoskeletal disorganization, cytoplasmic redistribution of ZO-1 and aberrant mitotic figures. [score:3]
No significant differences in miR-205 and miR-373 expression were identified in paired colonic tumor tissue and corresponding normal mucosa from patients with conventional colonic adenocarcinoma (non-mucinous). [score:3]
We used Ingenuity Pathway Analysis (IPA) to build a hypothetical signaling mo del based on these molecules differentially expressed in Caco-2 [WT]/miR-205 vs. [score:3]
Expression levels of miR-205 and miR-373 are increased in mucin-producing human colon cancers. [score:3]
Stable overexpression of miR-205 in Caco-2 [WT] induced formation of secretory cells containing large vesicles with pale lucent contents occupying almost the entire cytoplasm (Fig 2A). [score:3]
In contrast, no significant differences in miR-205 and miR-373 expression are observed between paired conventional CRC (n = 18) tumor tissue and corresponding normal mucosa. [score:3]
We show in patients that elevated expression levels of miR-205 and miR-373 are associated with mucinous colon cancers and mucin-producing UC-colon cancers, but not with sporadic colonic AC that lack mucinous components. [score:3]
S4 FigExpression levels of (A) miR-205, (B) miR-373, (C) miR-1, (D) miR-10a and (E) miR-133a in different human colonic adenocarcinoma cell lines (LS 174T, HT-29, HCT 116 and SW480), in comparison to naïve (untransfected) Caco-2, Caco-2 [WT] and Caco-2 [D299G] cells, as determined by qPCR (n ≥ 2 samples/cell line). [score:3]
Expression levels of miR-205 and miR-373 were specifically increased in the two subgroups of colonic adenocarcinoma associated with mucin production (mucinous and chronic UC-related colorectal cancers) relative to adjacent normal colonic mucosa (Fig 1A and 1B). [score:3]
Expression of miR-205 and miR-373 differentially (A) alters actin cytoskeletal architecture, influences (B) ZO-1 and (C) phospho-β-CATENIN -associated barrier integrity, and (D) induces formation of multinucleated cells with multipolar spindles. [score:3]
Among the 2–7 remaining candidates per plasmid, individual subclones were chosen based on best expression levels of mature miR-205 and miR-373 using qPCR analysis. [score:3]
Abundant mucin production and MUC2 expression, which represent key features of goblet cells and MAC, were enhanced by miR-205 signaling. [score:3]
Expression levels of miR-205 and miR-373 in human CRC patient samples and Caco-2 subclones. [score:3]
Overexpression of miR-205 and miR-373 differentially alter morphological features of intestinal epithelial barrier integrity. [score:3]
However, we did not identify any correlations between miR-205 and miR-373 expression levels and cancer stages (including histological grade) in any subtype. [score:3]
Future studies must determine whether such mutations may influence activity and outcome of miR-205/miR-373 signaling and whether aberrant TLR4 signaling may be directly involved in MAC pathogenesis. [score:3]
Of note, conditioned media from Caco-2 [D299G] stimulated enhanced expression of miR-373, but not miR-205, in Caco-2 [WT] (Fig 5D). [score:3]
Reversely, the conditioned media from Caco-2 [D299G] induced expression of miR-373, but not miR-205, in Caco-2 [WT], suggesting that secretory products from the tumor cells may have the capacity to promote miR-373 signaling in a paracrine/autocrine manner, which may contribute to malignant transformation. [score:3]
0156871.g002 Fig 2(A-D) Caco-2 [WT] overexpressing miR-205 or miR-373 display significant morphologic changes when compared to control Caco-2 [WT]/miR-c. In contrast, suppression of miR-373 reverses some of the neoplastic characteristics of Caco-2 [D299G]. [score:2]
Of note, expression of miR-205 was slightly higher in UC -associated cancer compared to (non-UC) mucinous cancer. [score:2]
miR-205 promotes goblet cell differentiation and cell cycle regulation. [score:2]
Functionally, miR-205 directs the intestinal epithelial cell fate decision toward a mucin-producing goblet cell-like lineage and miR-373 drives inflammation -associated tumor progression by decreasing cell-cell adhesion and increasing invasion. [score:2]
Collectively, our findings imply that miR-205 activates a complex regulatory circuit whose orchestration induces enhanced mucinous differentiation in colonic epithelial cells. [score:2]
Signaling via miR-205 and miR-373 can favor epithelial-to-mesenchymal transition (EMT) and cancer cell migration in certain tumor entities [24, 31– 33]. [score:1]
miR-205 and miR-373 disturb intestinal epithelial barrier integrity. [score:1]
However, the possible roles of miR-205 and miR-373 in CRC pathogenesis remain so far unknown. [score:1]
In contrast, activation or inactivation of miR-205 did not influence the invasive migration pattern. [score:1]
Caco-2 [D299G]/α-miR-205, which is shown in Fig 4C. [score:1]
Next, we aimed to determine the effects of miR-205 and miR-373 on cellular biology and function in normal and neoplastic intestinal epithelium in-vitro. [score:1]
To further understand the morphologic changes induced by miR-205 and miR-373, we performed a series of immunofluorescence staining experiments to assess the effects on structural organization of the actin cytoskeleton (Fig 3A), distribution of barrier -associated tight junctional ZO-1 (Fig 3B) and phospho-β-CATENIN (Fig 3C) and formation of the mitotic spindle (Fig 3D). [score:1]
Recently, independent reports have variably reported miR-205 and miR-373 to be associated with CRC [21– 23], but individual cases were not classified into histological subtypes. [score:1]
We found that PKCε was repressed in Caco-2 [WT]/miR-205, which was associated with enhanced AKT phosphorylation (Fig 4A). [score:1]
In conclusion, to the best of our knowledge, this study provides first evidence that miR-205 and miR-373 may correlate with mucinous CRC in humans and functionally induce different features of mucinous -associated neoplastic progression in Caco-2 subclones. [score:1]
miR-205 interacts with members of the miR-200 family (miR-200a/-200b) [24] and represents an epithelial-specific miRNA [25], essentially involved in normal cell functions, such as regeneration and stem cell expansion [26]. [score:1]
We investigated the role of miR-205 and miR-373 in the pathophysiology of different histological subtypes of colorectal cancer by assessing their expression, together with that of other miRNAs, in specimens of conventional, mucinous and UC -associated human colonic adenocarcinoma. [score:1]
0156871.g006 Fig 6. Functional analysis of miR-205 and miR-373 in colon cancerogenesis. [score:1]
Our results indicate that miR-205 and miR-373 may differentially contribute to the aggressive behavior of mucinous malignancy in CRC. [score:1]
Thus, we provide first evidence that distinct signaling effects of miR-205 and miR-373 may differentially contribute to the unique phenotype of MAC in CRC. [score:1]
We tested the single miRNAs individually, and not the combined miR-205/miR-373 phenotype. [score:1]
Functional analysis of miR-205 and miR-373 in colon cancerogenesis. [score:1]
Both KLF4 and TGFβ1 induce cell cycle arrest via CYCLIN D2 [48, 49], which was also increased by miR-205 in Caco-2 [WT]. [score:1]
Functionally, miR-205 conferred resistance to chemotherapy of goblet cell-like Caco-2 [WT], potentially through enhanced secretion of MUC2 [50]. [score:1]
Forced introduction of miR-205 into normal-like Caco-2 [WT] conferred a gain-of-function phenotype, leading to accumulation of mucus-secreting goblet cell-like cells, which strikingly resembled the mucinous component of MAC. [score:1]
Both miR-205 and miR-373 seem to exert pleiotropic effects on tumorigenesis, depending on the cell or tissue of origin. [score:1]
miR-205 and miR-373 drive different functions of colon cancer progression. [score:1]
miR-205 induces increased mucin production, while miR-373 causes dedifferentiation. [score:1]
analysis confirmed increased production of MUC2 in Caco-2 [WT]/miR-205 (Fig 2D). [score:1]
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We validate this relation in vivo, showing that tissue-specific ERβ knockouts downregulate miR-205 expression in the luminal surface of the inner colon (Figure 4), and that that expression levels of PROX1 were inversely correlated with ERβ or miR-205 (Supplementary Table S1). [score:9]
We test whether ERβ silences PROX1 expression through the upregulation of miR-205 and explore the functional effects of this regulation. [score:7]
We demonstrate that ERβ transcriptionally upregulates miR-205 (Figure 2) and that miR-205, subsequently, represses PROX1 expression through direct interaction with its 3′UTR (Figure 3). [score:7]
ERβ upregulates miR-205 expression in colon cancer cells. [score:6]
Thus, we conclude that ERβ inhibits both invasion and metastatic potential of colon cancer cells through its upregulation of miR-205 in vitro and in vivo. [score:6]
Figure 3(A) PROX1 mRNA levels are downregulated by miR-205 overexpression in colon cancer. [score:6]
Accordingly, miR-205 inhibitors, which block the activity of mature miR-205, increased PROX1 levels in cell lines that express miR-205 (SW480-ERβ and HCT116-ERβ cells, Figure 3C). [score:5]
As detailed in Supplementary Table S1, expression of both ERβ and miR-205 were inversely correlated with Prox1 (p = 0.037, and p = 0.048) while ERβ and miR-205 expression were positively correlated (p = 0.028). [score:5]
In the literature, the role of miR-205 appears cell dependent, as it can act both as an oncogene promoting tumor initiation and growth, or as a tumor suppressor inhibiting cell proliferation and invasion (reviewed in [28]). [score:5]
To demonstrate that the dysregulation of miR-205 and PROX1 occurs as a result of lost ERβ expression in vivo, we generated intestine-specific ERβ knockout mice (ERβ [I KO]). [score:5]
Using 3′UTR-luciferase-reporter assay we demonstrated that the activity of luciferase cloned with a PROX1 wild-type 3′UTR was significantly reduced by miR-205 expression, while its activity was unaffected in the clone with a mutation in the putative 3′UTR target site (Figure 3E). [score:5]
SW480-ERβ and HT116-ERβ cells were transiently transfected by miR-205 inhibitors or inhibitor control at the final concentration of 50 nM, followed by qPCR analysis after 48 h. Experiment replicated two times. [score:5]
Furthermore, as more potential sites are predicted in the 3′UTR of PROX1 (Supplementary Figure S2), miR-205 may interact at multiple sites to regulate PROX1 translation. [score:4]
We conclude that ERβ, utilizing its DNA -binding capacity, transcriptionally upregulates miR-205. [score:4]
To explore whether PROX1 may be a direct target of miR-205, we used miRanda prediction software to scan the 3′UTR of human PROX1 gene in search of a miR-205 binding site. [score:4]
Thus, miR-205 repress PROX1 expression directly through binding to its 3′UTR sequence. [score:4]
ERβ upregulated miR-205 in all cell lines (Figure 2B), consistent with our previous observation in SW480 cells. [score:4]
miR-205 directly silences PROX1 by targeting its 3′UTR. [score:4]
Next, as ERs can bind to cis-regulatory DNA elements either directly through its DNA -binding domain (DBD) or via a tethering mechanism, we tested whether an ERβ mutated in the DBD (ERβ-mDBD) would regulate miR-205. [score:4]
We found that as ERβ disappeared, miR-205 levels were also significantly downregulated (p = 0.05, Figure 4C), while Prox1 levels showed a trend of being increased (Figure 4D). [score:4]
ERβ upregulates miR-205 in several colorectal cancer cell lines. [score:4]
We propose that the upregulation of miR-205 and subsequent repression of PROX1 is important beneficial effects of ERβ activity in the colon, and that the resulting combination of reduced cell proliferation and metastasis is a powerful mechanism. [score:4]
ERβ through miR-205 inhibits cell invasion in vitro and in vivo Using transwell invasion assay we found that, consistent with the increase of cell adhesion capacity above and previously reported inhibition of migration in SW480 [21], ERβ significantly reduced cell invasion of both SW480 and HT29 cells (Figure 7A, left). [score:4]
We show that expression of miR-205 mimic also resulted in increased adhesion (Figure 6E). [score:3]
The inverse relationship between miR-205 and PROX1 mRNA levels imply that miR-205 may reduce PROX1 expression. [score:3]
miRNA-205 target prediction. [score:3]
ERβ and miR-205 inhibits tumor invasion in vitro and in vivo. [score:3]
Expression of ERβ, miR-205, and PROX1 in human colon tissues and cells. [score:3]
Our previous studies showed that expression of ERβ resulted in increased miR-205 levels [21], and decreased PROX1 levels [23], in SW480 colon cancer cells. [score:3]
ERβ through miR-205 inhibits cell invasion in vitro and in vivo. [score:3]
In different human colon cancer cell lines, we observed a clear inverse expression of miR-205 and PROX1 protein (Figure 1C). [score:3]
The 8-nucleotide seed sequence of miR-205 showed complete complementarity to a target site at position 291–313 of the PROX1 3′UTR (Figure 3D and Supplementary Figure S2). [score:3]
Expression of miR-205 also generated more adhesiveSW620 cells. [score:3]
Consistently, cell cycle analysis showed that the population of cells remaining in G0 was increased and the population undergoing DNA synthesis and G2/M stage was reduced in a similar manner by either ERβ or miR-205 expression (Figure 5C). [score:3]
Figure 6(A) EMT markers and PROX1-regulated genes FN1 and SNAIL are regulated by both ERβ and miR-205 in SW480 and HT29 cells. [score:3]
Our findings are consistent with the expression data from human clinical samples above, and corroborate the ERβ/miR-205/Prox1 mechanism in normal colon epithelia in vivo. [score:3]
Figure 7ERβ and miR-205 inhibits tumor invasion in vitro and in vivo(A) Cell invasiveness is reduced by ERβ and miR-205. [score:3]
Sequence alignment between PROX1 3′UTR and mature miR-205 was performed using miRanda and Targetscan algorithms. [score:3]
ERβ-mDBD failed to increase miR-205 levels in both SW403 and SW620 cells (Figure 2B), suggesting this regulation is dependent on direct DNA binding. [score:3]
However, the results were divergent for some experiments: transient expression of ERβ did not increase the adhesion of SW403 or SW620 cells, and we did not notice increased adhesion by miR-205 mimic in SW480 or HT29 cells (data not shown). [score:3]
Labeled SW480 and HT29 cells, with and without ERβ expression, or with and without transfection of miR-205 mimic, were injected into transgenic Tg(kdrl:EGFP)mitfab692 zebrafish larvae in three independent experiments and observed for metastatic potential after 24 and 48 hpi. [score:3]
We injected fluorescence-labeled SW480 and HT29 cells, with and without ERβ expression, and with or without miR-205 mimic, into transgenic zebrafish larvae, and observed the metastatic potential of these cells. [score:3]
Finally, to demonstrate that upregulation of miR-205 is a consequence of transcriptional regulation and not miRNA post-transcriptional processing, we measured the primary transcript (pri-miR-205). [score:3]
Supplementary Table S1 shows the corresponding correlation between ERβ, miR-205, and PROX1 expression. [score:3]
We have previously found that the level of the microRNA (miRNA) miR-205, is increased upon expression of ERβ in SW480 cells [21]. [score:3]
Tissue-specific knockout of ERβ decreases miR-205 and increases Prox1 in the colon epithelial cells of mice. [score:2]
Both ERβ and miR-205 have been suggested to regulate epithelial cell differentiation and EMT in different tissues [11, 29]. [score:2]
Here, we show that miR-205 is anti-proliferative in colon cancer cells, and we suggest that this regulation contributes to ERβ's anti-proliferative effect (Figure 5). [score:2]
To investigate whether ERβ can directly increase miR-205 levels, we tested three more cell lines: HT29, SW403 and SW620, before and after re -expression of ERβ. [score:2]
This function of miR-205 is, however, not dependent on its ability to repress PROX1, as PROX1 does not directly affect the proliferation of colon cancer cells [25]. [score:2]
Our data show that miR-205 is anti-proliferative in colon cancer cells, and indicate that its regulation contributes to the anti-proliferative effects of ERβ. [score:2]
The mutant human PROX1 3′UTR is represented in the lower panel and the disruption of base-pairing is indicated by X. (E) miR-205 directly interacts with the 3′UTR of PROX1. [score:2]
ERβ and miR-205 modulate CD24/CD44 cell populations and adhesion in colon cancer cells. [score:1]
Therefore, as ERβ and miR-205 repress PROX1, we evaluated whether they impacted expression of different mesenchymal and adhesion markers in colon cancer cells. [score:1]
Thus, while our data are not fully consistent, taken together, it supports that ERβ and miR-205 increase adhesion and therefore, may lessen invasion and/or metastatic potential of colon cancer cells. [score:1]
ERβ decreased the CD44 -positive population in SW480 and HT29 cells, miR-205 decreased the CD44 -positive population in SW480 cells, and siPROX1 decreased the population in HT29 cells (Figure 6C– 6D). [score:1]
SW480-ERβ and HT29-ERβ cells were transfected with 50 nM of miR-205 mimic or scrambled mimic control in three replicates, followed by qPCR analysis 48 h after transfection. [score:1]
ERβ and miR-205 reduce cell proliferation. [score:1]
was performed 72 h after ERβ or miR-205 mimic transfection, and all experiments were replicated three times. [score:1]
Similar results were noted upon miR-205 transfection (Figure 7A, right). [score:1]
miR-205 has been reported to affect cell proliferation in different types of cancer [28], but little is known of its effect in colon cancer. [score:1]
As PROX1 is known to increase invasiveness [35], its repression by ERβ and miR-205 should be important in relation to colon tumor progression and invasion. [score:1]
Both ERβ and miR-205 block cell proliferation. [score:1]
The functions of ERβ and miR-205, as detailed in this study, reinforce the protective role of ERβ in colon cancer. [score:1]
Levels of miR-205, and Prox1 were examined using qPCR. [score:1]
The function of miR-205 is relatively unknown in colon cancer, but low levels correlate with increased invasion into lymphatic vessels [22]. [score:1]
The role of miR-205 in colorectal cancer is relatively unknown, and miR-205 has been suggested to play dual roles in carcinogenesis [37]. [score:1]
In this study, we describe a putative miR-205 binding site in the 3′UTR of PROX1, and we propose that this is a key mechanism behind the estrogen -mediated colorectal cancer-protective effect. [score:1]
Similarly, miR-205 transfection reduced the metastasis potential to only 9% and 6%, respectively (p = 0.006 and p = 0.001, respectively). [score:1]
Highlighted nucleotides indicate the seed sequence of miR-205. [score:1]
Both ERβ and miR-205 exhibited a significant (p < 0.05) anti-metastatic potential in both cell lines. [score:1]
mRNA levels were analyzed 48 h after miR-205 double transfection, and experiments were replicated two times. [score:1]
We found that pri-miR-205 is strongly elevated by ERβ in SW480 (Figure 2C). [score:1]
Relative miR-205 levels were determined using qPCR and PROX1 protein levels using western blot. [score:1]
Loss of ERβ is accompanied by loss of miR-205 and increased PROX1 levels in primary colorectal cancer specimens. [score:1]
This is accompanied by decreased miR-205 and increased PROX1. [score:1]
SW480 and HT29 cells with and without ERβ and miR-205 mimic were labeled in vitro with 2μM of lipophilic dye CM-Dil (Invitrogen) and 500 cells were injected into the yolk of zebrafish larvae at 48 h post-fertilization (hpf), followed by incubation at 32°C. [score:1]
In addition, our results suggest that miR-205 replacement therapy is an avenue to explore in an effort to combat colon cancer metastasis. [score:1]
Intestinal-specific KO of ERβ results in decreased miR-205 in colon epithelial cells. [score:1]
In metastatic colorectal cancer, miR-205 levels have been reported to be reduced [22], suggesting that its downregualtion is advantageous for metastatic cells. [score:1]
In the same data set, miR-205 levels are also reduced in the tumors (Figure 1A, middle panel), while PROX1 levels are increased (Figure 1A, right panel). [score:1]
Human wild-type or mutant PROX1 3′UTR were cloned downstream of the firefly luciferase gene in the pEZX-MT01 vector (Genecopoeia, Rockville, MD, USA) and co -transfected with miR-205 mimic or control mimic (both from Dharmacon, 30 nM) in HEK293 cells using Lipofectamine 2000 (Invitrogen), according to the manufacturer's protocol. [score:1]
Protein was extracted 72 h after single miR-205 mimic or scrambled mimic control transfection and β-actin was used as loading control. [score:1]
miR-205 mimic treatment (Figure 6A) further reduced their levels, indicating ERβ and miR-205 may attenuate EMT in colon cancer. [score:1]
The full-length mRNA sequence of human PROX1 (ENSG00000117707, NM_002763) and mature human miR-205 sequence were obtained from Ensembl and miRBase dataset, respectively. [score:1]
Upon injecting SW480 and HT29 cells into zebrafish embryos we observed clear and consistent anti-metastatic effects of both ERβ and miR-205 in vivo. [score:1]
Cells were analyzed 48 h after single miR-205 mimic and siR-PROX1 transfection, and experiments were replicated two times. [score:1]
We here demonstrate that miR-205 mimic treatment also reduces the BrdU -positive cell population in SW480 and HT29 cells (Figure 5B). [score:1]
ERβ and miR-205 affects EMT, stemness and cell adhesion in colon cancer. [score:1]
Recent studies have attributed anti-proliferative effects of miR-205 in mammary stem cell fate [38], and in gastric cancer [39]. [score:1]
HEK293 cells were co -transfected with wild-type or mutant PROX1 3′UTR luciferase construct (800 ng), and miR-205 mimic or scrambled mimic control (50 nM). [score:1]
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Other miRNAs from this paper: hsa-mir-205, hsa-mir-214, mmu-mir-214, hsa-mir-494, mmu-mir-494
Therefore, we hypothesized that some tumor suppressor genes targeted by miR-205 are downregulated in OC as miR-205 was upregulated in OC. [score:11]
Finally, SMAD4 and PTEN were selected for further study since these two genes were found to be the lowest expression in both HO-8910 and S KOV-3 cells overexpressing miR-205, and also have been reported to be down-regulated in OC previously and is closely involved in OC cell proliferation, migration, invasion and chemoresistance. [score:8]
Taken together, these data indicate that miR-205 can repress the expression of SMAD4 or PTEN in OC cells by directly targeting the 3′ UTR of SMAD4 or PTEN mRNA. [score:6]
Our data showed that miR-205 was upregulated in OC tissues and cells in comparison to the controls, and miR-205 overexpression was significantly associated with poor overall survival in OC patients. [score:6]
MiR-205 was upregulated in ovarian cancer and overexpression of miR-205 promoted ovarian cancer cell proliferation, metastasis both in vitro and in vivo. [score:6]
Furthermore, the function of miR-205 in ovarian cancer may be exerted via downregulation of the target genes SMAD4 and PTEN, which play an important role in the function of miR-205 in ovarian cancer. [score:6]
Furthermore, the cisplatin-resistant OC cells S KOV-3/DDP showed a significant higher expression of miR-205, and lower PTEN expression compared with its parent cancer cells S KOV-3. Therefore, these findings showed that miR-205 could be a new member of the miRNAs that were involved in ovarian cancer cisplantin resistance, which was involved in AKT signal pathway through targeting PTEN. [score:6]
6) mice with higher miR-205 expression had lower expression of SMAD4 and PTEN than that of controls. [score:5]
Next, to verify the high expression of miR-205 in ovarian cancer patients, miR-205 expression of 110 ovarian cancer tissues paired with three normal ovarian tissues were detected by qRT-PCR. [score:5]
Therefore, we predicted potential targets of miR-205 by bioinformation analysis and several target genes were identified. [score:5]
From the miRWALK, hundreds of potential targets were found to be targeted by miR-205. [score:5]
How to cite this article: Li, J. et al. Upregulation of MiR-205 transcriptionally suppresses SMAD4 and PTEN and contributes to human ovarian cancer progression. [score:5]
The mice group that stably overexpressing miR-205 expressed significantly higher luciferase luminescence activities. [score:5]
Taken together, these results strongly suggest that miR-205 is correlated with poor prognosis, and is upregulated in ovarian cancer, suggesting that miR-205 functions as an oncogene in ovarian cancer development. [score:5]
But it is unclear whether and how these confirmed miRNAs such as miR-205, miR-494, miR-214 directly targeting PTEN co-regulate the PTEN/Akt pathway, further effects the DDP resistance and other biological function in a collaborative or antagonistic manner. [score:5]
In our study, we demonstrated that overexpression of miR-205 led to an obvious cisplatin resistance in OC cells and is negatively correlated with PTEN expression. [score:5]
Among these genes, 14 tumor-suppressor genes were identified after reading literatures and then screened in our two stably expressing miR-205 cell lines (Supplementary Figure S1). [score:5]
SMAD4 and PTEN are direct target of miR-205 in OC. [score:4]
SMAD4 and PTEN are direct transcriptional targets of miR-205 in OC cells. [score:4]
Therefore, this research indicates that miR-205 may play an important role in ovarian cancer progression and could be targeted for the development of novel treatment for OC in the future. [score:4]
These finding suggested that miR-205 might act as an oncogene whose upregulation contributed to the progression and metastasis of OC. [score:4]
To confirm that SMAD4 or PTEN was directly inhibited by miR-205, a dual-luciferase reporter system was used. [score:4]
Moreover, another study showed that miR-205 was a suppressor of prostate cancer development, and loss of miR-205 was associated with prostate cancer progression 35. [score:4]
miR-205 is upregulated in ovarian cancer. [score:4]
MiR-205 inhibited the firefly luciferase reporter activity of wild-type SMAD4 and PTEN 3′ UTR, but this inhibition was less changed for 3′ UTR with mutated binding sites (Fig. 4E). [score:4]
Furthermore, overexpression of miR-205 could promote cell proliferation, migration, invasion and chemoresistance of ovarian cancer cells. [score:3]
Kaplan-Meier analysis indicated that the 5-year overall survival (OS) rates of ovarian cancer patients with high miR-205 expression was significantly lower (Fig. 1A). [score:3]
In agreement with these observations, upregulation of miR-205 was also confirmed in 6 ovarian cancer cell lines (HO-8910, HO-8910PM, S KOV-3, S KOV-3ip, S KOV-3/DDP, and COC1) compared with a pool of 3 normal ovarian tissues as a normal control (Fig. 1C). [score:3]
Overexpression of miR-205 also increased the chemoresistance of OC cells. [score:3]
First, endogenous SMAD4 and PTEN mRNA or protein levels were markedly decreased in HO-8910 and S KOV-3 cells stably expressing miR-205 compare to that of control cells (Fig. 4B,C). [score:3]
Establishment of stably expressing miR-205 ovarian cancer cell lines. [score:3]
We infected HO-8910 and S KOV-3 cells with lentiviral vector harboring miR-205 (LV-miR-205) to establish two stably expressing miR-205 cells. [score:3]
We detected miR-205 expression in 110 archived clinical ovarian cancer tissues. [score:3]
The HO-8910 cells (1 × 10 [6] cells) stably expressing either LV-miR-205 or LV-miR-Ctrl were injected intraperitoneally (i. p. ) into two groups. [score:3]
Moreover, High expression of miR-205 was also found in cervical cancer cell lines as well as clinical patient samples 33. [score:3]
In bladder cancer, miR-205 was found to be significantly upregulated compared to normal tissue 32. [score:3]
We examined the relationship between miR-205 expression and cell sensitivity to a chemotherapeutic drug, Cisplatin (Sigma-Aldrich, St. [score:3]
In accordance with this hypothesis, we found that ectopic expression of miR-205 decreased SMAD4 or PTEN both mRNA and protein levels in OC cells. [score:3]
MiR-205 is upregulated in OC and correlated with poor survival. [score:3]
HO-8910 cells stably expressing miR-205 or control cells were injected intraperitoneally (i. p. ) into nude mice in each group. [score:3]
These information suggesting that oncogenic activity of miR-205 is possible, in part, through targeting SMAD4 and PTEN. [score:3]
Overexpression of miR-205 significantly promoted tumor dissemination. [score:3]
Thus, to predict potential miR-205 targets, we used the miRWALK (http://zmf. [score:3]
Consistent with above results, there was also a negative correlation between miR-205 expression and mRNA or protein levels of PTEN in S KOV-3/DDP and S KOV-3 cells (Fig. 4D). [score:3]
The result showed that miR-205 was significantly overexpressed in ovarian cancer tissues (Fig. 1B). [score:3]
In our study, the tumor-promotive role of miR-205 in vivo was treated by intraperitoneally injecting HO-8910 cells stably expressing miR-205 and monitored by IVIS system. [score:3]
The migration assay demonstrated that HO-8910 and S KOV-3 cells overexpressing miR-205 were found to have significantly higher rate of migration than control cells (Fig. 2D). [score:2]
Our study is the first to show that miR-205 functions as a tumor-promotive miRNA through directly binding to SMAD4 and PTEN in OC. [score:2]
Furthermore, qRT-PCR analysis of the implanted tumors showed that SMAD4 and PTEN mRNA expression were significantly reduced in the LV-miR-205 group compared with the LV-miR-Ctrl group (Fig. 5D), further supporting the notion that miR-205 promoted OC tumorigenesis via SMAD4 and PTEN. [score:2]
Similarly, the Matrigel invasion assay indicated that overexpression of miR-205 significantly promoted the invasiveness of HO-8910 and S KOV-3 cells (Fig. 2E). [score:2]
Further qRT-PCR analysis indicated the negative regulation of miR-205 to SMAD4 or PTEN. [score:2]
Overexpression of miR-205 led to an obvious increase in the IC50 value of cisplatin in both HO-8910 (IC50; miR 15.69 ± 1.05 control 7.35 ± 1.04) and S KOV-3 cells (IC50; miR 14.87 ± 1.03 control 9.22 ± 1.03) when compared with that in the control group (Fig. 3A). [score:2]
After this, miR-205 expression was further found to be higher in S KOV-3/DDP cells compared with that in S KOV-3 (Fig. 3C). [score:2]
We then examined the tumor promotive role of miR-205 in ovarian cancer progression using an in vivo tumor mo del. [score:1]
The wild-type or mutated 3′ UTR of SMAD4 and PTEN mRNA were inserted downstream of the luciferase reporter gene, and LV-miR-205 was co -transfected with each construct in HEK-293T cells. [score:1]
Both SMAD4 and PTEN mRNAs had one possible binding site for miR-205 (Fig. 4A). [score:1]
In summary, this study identified miR-205 as a novel oncogenic miRNA that is stimulated in both in vitro and in vivo studies in OC. [score:1]
Having observed the association of miR-205 expression and poor survival in OC patients, we set out to functionally characterize the effects of miR-205 on ovarian cancer cells. [score:1]
We counted the number of peritoneal implants and found that the implants number in LV-miR-205 group were significantly more than that in LV-miR-Ctrl group (Fig. 5C). [score:1]
To our knowledge, the role and mechanism of miR-205 in OC have not been completely understood. [score:1]
To further verify the promoting effect of miR-205 on cell chemoresistance, we also detect miR-205 expression in the cisplatin-resistant S KOV-3/DDP cells and its parent cancer cells S KOV-3. First, using the sulforhodamine B (SRB) assay, we proved that S KOV-3/DDP cells were indeed significantly more resistant to the therapy of cisplatin compared with S KOV-3 (IC50; S KOV-3/DDP 35.67 ± 1.06 S KOV-3 9.27 ± 1.03) (Fig. 3B). [score:1]
miR-205 promotes the chemoresistance of OC cells. [score:1]
miR-205 promotes OC tumorigenesis in vivo. [score:1]
We then used the Cell Counting Kit-8 (CCK-8) assay to assess the effects of miR-205 on cell proliferation, the result showed that miR-205 overexpression significantly increased the growth rates of HO-8910 and S KOV-3 cells (Fig. 2B), and the promoting effect of miR-205 on cell proliferation was further confirmed by colony formation assay (Fig. 2C). [score:1]
To our knowledge, there is no study on miR-205 and OC tumorigenicity in an animal mo del. [score:1]
For the detection of miR-205, RNA was reverse transcribed into cDNA using All-in-One™ miRNA First-Strand cDNA Synthesis Kit (GeneCopoeia, Guangzhou, China), and then was used to perform qRT-PCR using All-in-One miRNA qRT-PCR Detection Kit (GeneCopoeia, Guangzhou, China). [score:1]
MiR-205 promotes OC cell proliferation, migration and invasion in vitroHaving observed the association of miR-205 expression and poor survival in OC patients, we set out to functionally characterize the effects of miR-205 on ovarian cancer cells. [score:1]
miR-205 promotes OC cell proliferation, migration and invasion in OC cell lines. [score:1]
In contrast, low levels of miR-205 is observed in head and neck squamous cell carcinomas and associated with increased recurrence and poor prognosis 34. [score:1]
Collectively, these data clearly show that miR-205 is a promoter of proliferation, migration and invasion in OC cells. [score:1]
However, the mechanisms underlying how miR-205 affects tumor progression were not clear. [score:1]
The 3′ UTR wild-type report plasmid or 3′ UTR mutant report plasmid of SMAD4 or PTEN were transfected into 293 T cells, and LV-miR-205 or LV-miR-Ctrl was co -transfected with each plasmid in 293 T cells. [score:1]
These finding suggest that miR-205 may play an important role in promoting carcinogenesis and chemoresistance of OC. [score:1]
MiR-205 promotes OC tumorigenesis in vivoWe then examined the tumor promotive role of miR-205 in ovarian cancer progression using an in vivo tumor mo del. [score:1]
This data thus prove that miR-205 promotes chemoresistance of OC cells. [score:1]
293 T cells were cultured in 24-well plates and co -transfected with 3′ UTR wt plasmid or 3′ UTR mut plasmid in the presence of either miR-205 or negative control. [score:1]
The lentivirus vectors containing firefly luciferase, LV-hsa-miR-205 or LV-hsa-miR-Ctrl, were obtained from GENECHEM (Shanghai, China). [score:1]
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MiR-205 reduces SMAD4 expression by directly targeting its 3. Expression of miR-205 is upregulated in NSCLC tissues and inversely correlated with SMAD4 expression. [score:13]
MiRNAs can inhibit or suppress various biological processes including cell proliferation by targeting proliferation-related genes [22], and Huang et al. [23] showed that in silico, SMAD4 was a target gene of miR-205; therefore, we hypothesized that miR-205 could inhibit SMAD4 expression by binding to the SMAD4 3′-UTR region. [score:13]
Taken together, the results suggested that miR-205 binds directly to the target site the 3′-UTR of SMAD4 in NSCLC cells to inhibit its expression. [score:8]
Figure 5Expression of miR-205 is upregulated in NSCLC tissues and inversely correlated with SMAD4 expression(A) Relative miR-205 levels in 52 NSCLC tissues (T) and paired noncancerous lung tissues (N). [score:8]
Furthermore, Gene Expression Omnibus set (GSE36681) showed that miR-205 expression was upregulated in human NSCLC tissues (Figure 5B). [score:8]
In conclusion, our study shows that miR-205 suppresses the expression of tumor suppressor gene SMAD4 promotes NSCLC cells growth in vitro and in vivo. [score:7]
All these data indicated that re -expression of miR-205 could promote lung cancer cell growth in vivo by inhibiting the expression SMAD4. [score:7]
SMAD4 expression is regulated by miR-205 through targeting its 3′-UTR in NSCLC. [score:6]
Our findings also highlighted the therapeutic potential of miR-205 in the treatment of NSCLC and supported the development of effective therapeutic strategies that target miR-205 (or its targets, such as SMAD4) via a genetic or pharmacological approach. [score:6]
In addition, the expression of p21 was increased in cell ectopically expressing miR-205 (Figure 7C). [score:5]
We found that overexpression of miR-205 mimics had no effect on cell apoptosis (Figure 7B), whereas ectopic expression of miR-205 led to a significant reduction in the number of cells in the G1 phase (Figure 7A). [score:5]
In addition, the resected tissues from the agomir -treated xenograft tumors were analyzed to verify PTEN and SMAD4 expression using IHC: consistent with the above observations, significant loss of SMAD4 expression was shown in miR-205 agomir group comparied with the NC group (Figure 9D). [score:5]
Overexpression of an miR-205 mimic inhibits NSCLC cell viability and proliferation. [score:5]
As shown in Figure 9A, the miR-205 agomir increased the expression of miR-205 significantly and decreased the expression of SMAD4. [score:5]
Figure 9Overexpressing miR-205 in lung carcinoma xenografts promotes tumor growth in vivo(A) QRT-PCR analysis of miR-205 levels and SMAD4 mRNA expression in excised tumors transfected with miR-205 agomir and NC agomir; U6 and β-actin were used as internal controls, respectively. [score:5]
In addition, another study showed that low miR-205 expression in mammary epithelial cells promoted EMT, while its overexpression repressed cancer cells stemness [14]. [score:5]
Moreover, overexpression of miR-205 reduced SMAD4 expression in NSCLC cells remarkably (Figure 6A). [score:5]
These findings indicated that the stimulation or inhibition of miR-205 expression, as well as its biological functions, might be tissue or cancer-type dependent. [score:5]
MiR-205 is significantly downregulated in NSCLC cell lines; therefore, an miR-205 agomir was prepared for replacement therapy. [score:4]
Furthermore, to determine the function of miR-205 in NSCLC, taking into account that miR-205 is downregulated significantly in NSCLC cell lines [27, 28], we overexpressed miR-205 in NSCLC cells using miR-205 mimics and then evaluated the effect of miR-205 on cell growth (Figure 6A). [score:4]
MiR-205 is significantly downregulated in NSCLC cell lines [24, 25]; therefore, we only transiently cotransfected the reporter construct with miR-205 mimics into A549 cells. [score:4]
SMAD4 mRNA expression in A549 cells transfected with miR-205 mimics or NC. [score:3]
Thus, it remains important to understand thoroughly the molecular mechanisms underlying the differential biological effects and targets of miR-205 in NSCLC and other cancer types. [score:3]
The y-axis represents the log10 transformed fold change of T/N expression ratios of miR-205 levels and SMAD4 mRNA. [score:3]
In the present study, miR-205 expression was increased while SMAD4 was decreased in NSCLC, such that that the ratio of miR-205 level (T/N) was inversely correlated with that of the SMAD4 mRNA level (T/N) in 52 paired tissues (P = 0.0065). [score:3]
The results showed that the miR-205 mimics significantly inhibited the luciferase activity in cells transfected with the wild-type SMAD4 3′-UTR but did not repress the luciferase activity in cells containing the mutant construct (Figure 4B). [score:3]
Our results indicated the importance of miR-205 as a potential target in clinical therapy and demonstated that this miRNA merits further investigation as a promising gene therapy target to treat NSCLC. [score:3]
For example, miR-205 suppresses cell migration and invasion via the epithelial-to-mesenchymal transition in human prostate and breast cancer cells [13, 34], In support of its oncogenic function, miR-205 was binds to PETN and PHLPP2 to modulate PI3K/AKT signaling and promote cell proliferation in NSCLC [12]. [score:3]
A549 cells and stable cell lines overexpressing SMAD4 were plated in 6-well plates under normal culture conditions, and then transfected with si-SMAD4 and NC or miR-205 mimics. [score:3]
Interestingly, we also observed lower expression of miR-205 in adenocarcinomas than in squamous cell lung carcinoma (Table 1). [score:3]
Overexpression of miR-205 accelerates the cell cycle in NSCLC cells. [score:3]
Overexpression of an miR-205 mimic had no effect on cell apoptosis, but promoted the cell cycle in NSCLC cells. [score:3]
We next sought to clarify the cellular mechanisms underlying miR-205 -mediated tumor suppression. [score:3]
Further analysis showed that 42 NSCLC tissues had high miR-205 level while 37 tissues (88.1%) had low expression of SMAD4 mRNA. [score:3]
Eight NSCLC tissues had low miR-205 level, while three tissues (37.5%) had high expression of SMAD4 mRNA (Figure 5D). [score:3]
The primary tumors and adjacent normal tissues in a cohort of 52 patients were analyzed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) for the expression of miR-205 and SMAD4. [score:3]
mRNA expression values of Smad4 and miR-205 were normalized to the internal controls ACTB and U6, respectively. [score:3]
The x and y-axes represent the log10 transformed fold change of T/N mRNA expression ratios of miR-205 and SMAD4, respectively. [score:3]
To determine how miR-205 promotes cell proliferation in NSCLC cells, we examined cell apoptosis and the distribution of cell cycle phases in A549 cells overexpressing miR-205 and NC. [score:3]
The miR-205 level is increased in NSCLC tissues and ectopic miR-205 expression can promote NSCLC cell proliferation. [score:3]
Differences in miR-205 and SMAD4 expression between NSCLC tissues (T) and adjacent noncancerous lung tissues (N) were analyzed using a paired t test (two-tailed). [score:3]
The above studies suggested that miR-205 acts either as an oncogene or tumor suppressor gene, depending on the cellular environment. [score:3]
Overexpressing miR-205 in lung carcinoma xenografts promotes tumor growth in vivo. [score:3]
Briefly, a 215-bp fragment containing predicted miR-205 target site (positions 262–269) was chosen for the luciferase assay. [score:2]
Moreover, the expression of miR-205 was higher in squamous cell lung carcinoma compared with other types of NSCLC [10]. [score:2]
Dysregulation of miR-205 was observed in many types of tumors, including lung cancer [12]. [score:2]
As illustrated in Figure 5A, among 52 randomly selected paired tissues from NSCLC patients, miR-205 expression was significantly increased in tumor tissues compared with paired noncancerous tissues. [score:2]
miR-205 agomir and NC agomir (RiboBio Co, Ltd) were injected directly into the implanted tumor at a dose of 1 nmol (in 20 ml PBS) per mouse every 4 days, seven times. [score:2]
MiR-205 and SMAD4 mRNA levels are expressed as relative indexes normalized against U6 and β-actin, respectively. [score:2]
Considering the important functions of miR-205 and SMAD4 in NSCLC, the potential therapeutic use of miR-205 attracted our attention. [score:1]
Briefly, cells transfected with miR-205 mimics and si-SMAD4 or NC were diluted in complete culture medium and 200 cells were reseeded in a 60 mm plate. [score:1]
Clinical characteristics and levels of miR-205 and Smad4 mRNA expression in NSCLC tissues. [score:1]
Interestingly, the ratio of miR-205 level (Tumor/Normal; T/N) was inversely correlated with the ratio of SMAD4 mRNA levels (T/N) in 52 paired tissues (P = 0.0065; Figure 5C). [score:1]
Bar charts showing clonogenic growth of A549 cells transfected with miR-205 mimics or NC. [score:1]
To test this possibility, we subcloned the SMAD4 3′-UTR, containing the putative miR-205 binding site (both the wild type and mutated sites, separately) into vector psiCHECK-2 (Figure 4A). [score:1]
Figure 6(A) QRT-PCR analysis of miR-205 levels in A549 cells transfected with miR-205 mimics or NC for 72 h. U6 was used as the internal control. [score:1]
Given the complexity of its function, it would be interesting to investigate the correlation miR-205 expression with the activity of the TGF-beta signaling pathway in NSCLC. [score:1]
Collectively, the results suggested that miR-205 promotes cell proliferation by accelerating NSCLC cell cycle. [score:1]
Figure 7(A) Flow cytometry cell cycle analysis of A549 cells with miR-205 mimics or NC. [score:1]
CCK-8 assays showed that NSCLC cells overexpressing miR-205 had significantly higher proliferation abilities compared with control cells (Figure 6B). [score:1]
Cells were transfected with miR-NC, miR-205, Si-NC or Si-SMAD4. [score:1]
Subsequently, A549 cells were plated in a 24-well plate and cotransfected with the wild-type or mutated plasmid, control pRL-TK plasmid and with either miR-205 mimics or miR -negative control (NC) using Lipofectamine 2000 (Life Technologies). [score:1]
Recently, it was demonstrated that loss of miR-205 promoted the epithelial to mesenchymal transition (EMT) during tumor progression [13]. [score:1]
According to the instructions of the Cell Cycle Analysis Kit (Beyotime, Shanghai, China), cells were cultured in 6-well plates, transfected with miR-NC, miR-205, Si-NC or Si-SMAD4 for 72 h. The cells were then collected, washed with cold phosphate-buffered saline (PBS), fixed in 70% ethanol at 4°C for 24 h, washed with cold PBS again and stained in a Propidium Iodide (PI)/RNase A mixture. [score:1]
Furthermore, to validate these observations, we also transfected miR-205 mimics into NSCLC cells and injected miR-205 agomirs into implanted tumors: similar results were observed. [score:1]
Predicted duplex formation between miR-205 and the wild-type or mutant of miR-205 binding site is indicated. [score:1]
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6
[+] score: 190
Other miRNAs from this paper: mmu-mir-10b, mmu-mir-221
Pathogenesis of endometrial cancer has been recently connected with alterations of micoRNAs expression and our previous studies detected several microRNAs that were up-regulated in endometrial cancer tissues, with miR-205 being one of the most highly up-regulated [4, 5, 6]. [score:9]
Significant inhibition of tumor growth was observed after second injection of miR-205-LNA -inhibitor and was continuously present until the 17 [th] experimental day (after seven dosages of miR-205-LNA -inhibitor). [score:7]
Luciferase activity was significantly increased 24 hours after co-transfection endometrial cancer lines with pLightSwitch_3′UTR reporter vector and miR-205-LNA -inhibitor, proving that the inhibitor was efficient, biologically available and functional within the cells of HEC-1-B and Ishikawa lines (Figure 1). [score:5]
We also demonstrated that systemic administration of miR-205-LNA -inhibitor was feasible and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals. [score:5]
In order to evaluate transfection efficiency of miR-205-LNA -inhibitor and assess its functional impact within studied cell lines (HEC-1-B and Ishikawa) we co -transfected miR-205-LNA -inhibitor or scramble control and pLightSwitch_3′UTR reporter vector containing optimized target sequence complementary to the miR-205-5p (based on miRBase 16) cloned downstream of RenSP luciferase gene. [score:5]
In vivo effects of systemic administration of miR-205-LNA -inhibitorIn order to assess in vivo effects of intraperitoneal administration of miR-205-LNA -inhibitor we observed treated animals for a total period of 32 days. [score:5]
The results were presented in Figure 4. Significantly lower expression of miR-205 was noted in kidneys collected from miR-205-LNA -inhibitor treated mice comparing to animals injected with PBS or scramble control (p = 0.002, post-hoc p < 0.05). [score:5]
In the presented study miR-205-LNA -inhibitor (LNA-i-miR-205) effectively inhibited proliferation of endometrial cancer cells in vitro [14]. [score:5]
In order to additionally evaluate transfection efficiency and assess, if the studied inhibitor had a functional impact within studied cell lines we co -transfected 1×10 [6] EC cells with 50nM miR-205-LNA -inhibitor or scramble control and 30 ng/μl of pLightSwitch_3′UTR reporter vector containing optimized target sequence complementary to the miR-205-5p (based on miRBase 16) cloned downstream of RenSP luciferase gene (Acitve Motif, Carlsbad, CA, US). [score:5]
Figure 3 In vivo effects of systemic administration of miR-205-LNA -inhibitor A. Subsequent measurements of tumor volume showed significant differences between miR-205-LNA -inhibitor, scramble control (LNA-i-miR-NC) and not treated animals (PBS), * p < 0.05 for miR-205-LNA -inhibitor vs. [score:5]
Zhang et al. suggested it could act through inhibiting phosphatase and tensing homologue protein and Su et al. found that miR-205 promoted tumor proliferation and invasion through targeting estrogen-related receptor gamma [13, 14]. [score:5]
On the basis of our in vitro studies and the findings presented by other authors we speculated that systemic delivery of miR-205-LNA -inhibitor could inhibit endometrial cancer growth in vivo. [score:5]
Such observation suggested that the inhibitory effect of LNA-i-miR-205 was not long–lasting in tumor tissue and that observed effects needed to be sustained by regular administration of the inhibitor. [score:5]
On the contrary, tumor tissues obtained from miR-205-LNA -inhibitor treated animals demonstrated higher miR-205 expression as compared to PBS and scramble control (p < 0.001, post-hoc p < 0.05) (Figure 4). [score:4]
A. HEC-1-B: 13% decrease in proliferation was noted 12 hours after transfection, 39% - 24 hours after transfection, 48% - 36 hours after transfection, 57% - 48 hours after transfection, 68% - 60 hours after transfection and 80% - 72 hours after transfection as compared to negative control (p values at 12 to 72h were: 0.004, 0.012, 0.032, 0.026, 0.014, 0.008); B. Ishikawa: 24% proliferation inhibition 12 hours after transfection and almost complete proliferation inhibition 24 hours after transfection (p values at 12 to 72h were: 0.0025, 0.0002, 0.0004, 0.0018, 0.01, 0.15); C. KLE: 97% decrease in proliferation ability 24h after transfection (p values at 12 to 72h were: 0.78, 0.001, 0.0008, 0.0003, 0.0005, 0.002); D. Effects on BrdU uptake: proliferation of Ishikawa cells was reduced by 40% (p values: LNA-i-miR-205 vs. [score:4]
miR-205-LNA -inhibitor and scramble control. [score:3]
In line with those findings Zhang et al. reported, that in Ishikawa cells PTEN was targeted by miR-205 and was decreased by transfection of miR-205 mimic [13]. [score:3]
In vivo effects of systemic administration of miR-205-LNA -inhibitor. [score:3]
Increased miR-205 expression at the end of the study was consistent with the observed acceleration of tumor growth, which occurred after cessation of treatment. [score:3]
Toxicity assessment of systemic administration of miR-205-LNA -inhibitor. [score:3]
Histological changes in liver encountered after treatment with miR-205-LNA -inhibitor. [score:3]
Higher-order inhibition of proliferation by LNA-i-miR-205 was observed in Ishikawa cells (Figure 2B). [score:3]
miR-205-LNA -inhibitor (LNA-i-miR-205) used in our study was custom designed to work effectively in human cells in vitro and in mice xenograft of human EC and had a following sequence: CCGGTGGAATGAAGG. [score:3]
Taken together, these results indicate that systemic delivery of miR-205-LNA -inhibitor could be a promising treatment strategy for endometrial cancer and warrants further studies in other animal mo dels. [score:3]
In order to assess in vivo effects of intraperitoneal administration of miR-205-LNA -inhibitor we observed treated animals for a total period of 32 days. [score:3]
Interestingly, we observed significantly higher expression of miR-205 in tumor tissues from treated animals. [score:3]
Based on our previous studies and results published by other authors we speculated that miR-205 exhibited pro–oncogenic properties in endometrial cancer, and therefore its inhibition with sequence-specific antagonism could be applied as a therapeutic measure in this disease [17]. [score:3]
It is therefore possible that response to miR-205 inhibition could be cell line specific in vivo and dependent on PTEN status. [score:3]
miR-205 inhibits proliferation of EC cells in vitro. [score:3]
Figure 2Antiproliferative effect induced by transient transfection of LNA-i-miR-205 in endometrial cancer cell lines compared to scramble control (LNA-i-miR-NC): assessed using xCELLigence technology A. HEC-1-B: 13% decrease in proliferation was noted 12 hours after transfection, 39% - 24 hours after transfection, 48% - 36 hours after transfection, 57% - 48 hours after transfection, 68% - 60 hours after transfection and 80% - 72 hours after transfection as compared to negative control (p values at 12 to 72h were: 0.004, 0.012, 0.032, 0.026, 0.014, 0.008); B. Ishikawa: 24% proliferation inhibition 12 hours after transfection and almost complete proliferation inhibition 24 hours after transfection (p values at 12 to 72h were: 0.0025, 0.0002, 0.0004, 0.0018, 0.01, 0.15); C. KLE: 97% decrease in proliferation ability 24h after transfection (p values at 12 to 72h were: 0.78, 0.001, 0.0008, 0.0003, 0.0005, 0.002); D. Effects on BrdU uptake: proliferation of Ishikawa cells was reduced by 40% (p values: LNA-i-miR-205 vs. [score:3]
However, except for the platelets count, which was elevated in the miR-205-LNA -inhibitor treated animals, the absolute CBC values remained in normal range. [score:3]
A. Subsequent measurements of tumor volume showed significant differences between miR-205-LNA -inhibitor, scramble control (LNA-i-miR-NC) and not treated animals (PBS), * p < 0.05 for miR-205-LNA -inhibitor vs. [score:3]
Functional impact of miR-205-LNA -inhibitor within studied cell lines. [score:3]
Mice were randomly divided into three groups (five animals in each group) and were treated with miR-205-LNA -inhibitor, scramble control or PBS, respectively. [score:3]
In conclusion, the presented study showed that LNA-i-miR-205 was a potent inhibitor of endometrial cancer growth in vitro, which was confirmed using four different endometrial carcinoma cell lines. [score:3]
miRNA expression studies performed in tissues collected from experimental animals revealed significantly decreased miR-205 levels in kidneys, and markedly (although not significantly) reduced in heart and liver of LNA-i-miR-205 treated mice. [score:3]
In our study, treatment with miR-205-LNA -inhibitor was linked to elevated hematocrit, red and white blood cells as well as platelets counts. [score:3]
miR-205 expression in mice tissues. [score:3]
Complete blood counts (CBC) were performed at the end of the experiment and revealed significantly higher levels of hematocrit, red blood cells, white blood cells and platelets as well as slightly lower levels of MCH and MCHC in miR-205-LNA -inhibitor treated animals in comparison to PBS control. [score:3]
scramble (p values on days 3-17 were: 0.7, 0.036, 0.04, 0.01, 0.045, 0.032, 0.043), # p < 0.05 for miR-205-LNA -inhibitor vs. [score:3]
Such phenomena could be explained by a rebound effect of largely increased miR-205 synthesis in tumor milieu after the period of decreased availability during inhibitor treatment. [score:3]
Based on our own results and findings presented by other authors we hypothesized that inhibition of miR-205 would decrease the growth of endometrial cancer. [score:3]
miR-205 expression was also lower in heart and liver tissues in treated group, however this difference was not statistically significant. [score:3]
In order to simulate the mode of treatment administration in humans and evaluate the potential of this therapeutic modality in translational setting, we decided to use systemic delivery of miR-205-LNA -inhibitor in immunodeficient mice. [score:3]
The transient transfection of LNA-i-miR-205 resulted in a significant inhibition of proliferation in all examined cell lines as compared to LNA-i-miR-NC. [score:2]
LNA-i-miR-NC – 0.002, LNA-i-miR-205 vs. [score:1]
A. PBS group-liver architecture within normal limits; B. LNA-i-miR-NC group-liver architecture within normal limits; C. LNA-i-miR-205 group-small group of hepatocytes necrosis with scattered mononuclear inflammatory cells; slides stained with H+E x 400. [score:1]
untreated – 0.007) and RL-95 cells by 36% (p values: LNA-i-miR-205 vs. [score:1]
Similar effects were depicted in KLE cells, in which anti-proliferative activity of LNA-i-miR-205 reached significant level 24 hours after transfection (Figure 2C). [score:1]
LNA-i-miR-205 or LNA-i-miR-NC were incubated with Lipofectamine RNAiMAX at concentration of 12 pmol after dilution in OptiMEM. [score:1]
The functional role of miR-205 in endometrial cancer has not been fully revealed. [score:1]
LNA-i-miR-NC – 0.04, LNA-i-miR-205 vs. [score:1]
Specificity of LNA-i-miR-205 activity in endometrial cancer cell lines. [score:1]
The above lesions were present in all animals of miR-205 group. [score:1]
Although few studies attempted to explore miR-205 roles in EC in vitro, to our knowledge this is the first report to investigate in vivo effect of systemic delivery of LNA -modified-miR-205 inhibitor in this malignancy. [score:1]
Secondly, it would be interesting to assess the dose dependent response to LNA-i-miR-205 in terms of tumor growth and systemic toxicity. [score:1]
Cg-Foxn1/cmdb mice with LNA-i-miR-205 did not cause any significant adverse or toxic effects as assessed by activity level, food and water intake and histology studies. [score:1]
To assess anti-proliferative activity induced by LNA-i-miR-205, we transfected HEC-1-B, Ishikawa and KLE cells and monitored cells proliferation for 72h using xCELLigence technology. [score:1]
Figure 5 A. PBS group-liver architecture within normal limits; B. LNA-i-miR-NC group-liver architecture within normal limits; C. LNA-i-miR-205 group-small group of hepatocytes necrosis with scattered mononuclear inflammatory cells; slides stained with H+E x 400. [score:1]
untreated – 0.0001), HEC-1B cells by 11% (p values: LNA-i-miR-205 vs. [score:1]
miR-205 expression was measured in tumors and in vital organs from the studied animals at the end of the experiment. [score:1]
This phenomenon was not seen in PBS and scramble control groups suggesting the possibility of a specific LNA-i-miR-205 mediated activity. [score:1]
Therefore in the present study we aimed to investigate in vitro and in vivo, if inhibition of miR-205 would limit proliferation of endometrial cancer cells. [score:1]
The systemic effects of miR-205-LNA -inhibitor could be reliably evaluated in vivo, as sequences of human and murine miR-205 are identical. [score:1]
This observation is also concordant with the findings of other research groups, as miR-205 was consistently found increased in endometrial cancer, both in endometrioid and serous types [5- 12]. [score:1]
Measurements of vital organs revealed significant increase of spleen weight, and a decrease of heart and uterus weights in the miR-205-LNA -inhibitor group comparing to PBS and scramble control. [score:1]
LNA-i-miR-NC – 0.026, LNA-i-miR-205 vs. [score:1]
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[+] score: 150
These published targets highlight a subset of highly significant miR-205 targets whose deregulation would be expected to make a profound impact in normal epithelial cell function. [score:6]
Although expression of miR-205 has been described in epithelial tissues, this is the first evidence showing expression of miR-205 in the stomach and pancreas in mice. [score:5]
While miR-205 expression has been described in epithelial tissues, a systemic view of its expression has not been studied previously [12], [13]. [score:5]
In these experiments, LNA -based in situ hybridization and qRT-PCR was performed to compare endogenous miR-205 expression from wild-type mice with the lacZ reporter expression data. [score:5]
While little in vivo data is available for miR-205, the tumor protein p63 has been found to regulate its expression and is also essential for mouse development and proper squamous epithelium differentiation and maintenance [19], [20]. [score:5]
In situ hybridization on gut sections from wild-type embryos show that miR-205 is expressed specifically in the non-glandular epithelial cells of the stomach (Fig 3F, G), complementing the lacZ expression data. [score:5]
Here we analyze the spatial and temporal expression of miR-205 during mouse embryonic development using an integrated LacZ reporter allele (Fig 1A) [21]. [score:4]
Given this growing body of literature, we sought to generate a miR-205 knockout (KO) to fully ascertain the expression profile of this miRNA and to develop a better understanding of its biological significance in vivo. [score:4]
Given the knockout runted phenotype and broad expression of miR-205 in several digestive organs, the possibility remains that digestive processes are being disrupted. [score:4]
miR-205 exhibited striking temporal and spatial epithelial expression patterns during embryonic development. [score:4]
In addition, several cell culture based reports have revealed a role of miR-205 in targeting several regulators of proliferation [16], [17], [18]. [score:4]
MiR-205, an intergenic miRNA, is abundantly expressed in the skin of E17.5 mice and has been detected in footpad epithelium, tongue, epidermis, and corneal epithelium, suggesting that it may be a stratified squamous epithelial specific miRNA [12], [13]. [score:3]
These results further emphasize the refined expression of miR-205 to stratified squamous epithelium and its derivatives. [score:3]
LacZ activity is a robust reporter of mature miR-205 expression. [score:3]
Moreover, miR-205 has been shown to target ZEB1 and ZEB2, mediators of epithelial to mesenchymal transition (EMT), in order to maintain an epithelial state [14], [15]. [score:3]
To identify miR-205 expression in developing organs, E14.5 lacZ- KO/+ whole mount embryos were analyzed, and lacZ activity was observed in the thymus, stomach, pancreas, ureters and bladder (Fig 2 A-C). [score:3]
A targeted miR-205-lacZ reporter is functional in mouse embryos. [score:3]
These data show an excellent correlation between lacZ activity and miR-205 levels, with abundant miR-205 expression in the skin, stomach and thymus. [score:3]
Expression of miR-205 in many of these tissues has not been previously described. [score:3]
To gain a finer resolution on miR-205 expression, whole mount X-gal staining of embryos was followed with paraffin embedded sectioning of selected tissues. [score:3]
Together, these data validate the miR-205-lacZ reporter analysis and suggest that miR-205 is not substantially post-transcriptionally regulated at these developmental time points for these tissues. [score:3]
In addition, miR-205 has been shown to regulate proliferation and is regulated by p63, which marks epithelial stem cells, suggestive a role of miR-205 in proper maintenance of the stem cell populations in the epithelium [18], [31]. [score:3]
Given that mir-205 expression has not been previously reported in the stomach and that there appears to be a strong and differential pattern of lacZ activity in this organ (Fig 2B), stomach sections were examined from X-gal-stained E18.5 LacZ- KO/+ embryos. [score:3]
miR-205 is expressed in squamous stratified epithelium derived organs. [score:3]
B. miR-205 is developmentally regulated. [score:3]
Altogether these data reveal a fine granularity of miR-205 expression profile in a broad set of squamous epithelial tissues. [score:3]
miR-205 exhibits temporal and spatially distinct embryonic expression. [score:3]
0076634.g001 Figure 1 A. Two targeting strategies were used for miR-205 analyses. [score:3]
A. Two targeting strategies were used for miR-205 analyses. [score:3]
These data support a role for miR-205 in squamous epithelium derived organs, suggested by a bevy of work aimed at delineating the targets and pathways affected by miR-205 activity. [score:3]
These data reveal an important role for miR-205 in stratified squamous epithelial-derived tissues, providing an in vivo mo del for further understanding the roles of a noncoding RNA in basic physiology and potentially in the context of human disease. [score:3]
The error bars shown are S. E. M. Tongue [T], nasal cavity [NC], whisker follicles [W], and salivary glands [Sm], oesophagus [O], trachea [Tr], stomach [S], glandular region of the stomach [G], non-glandular region of the stomach [NG]Analysis of E18.5 lung revealed a faint lacZ activity in the epithelial cells of bronchioles, suggestive of intermediate levels of miR-205 expression in bronchioles compared to the other lacZ -positive tissues (unpublished data). [score:2]
The ability to produce mature hair follicles suggests that miR-205 plays a role in epidermal development after its differentiation from the multipotent progenitor population. [score:2]
In situ hybdrization was done using LNA-probes against miR-205 (Exiqon) according to the manufacturer's directions with the following modifications: Post-hybridization washes: 2xSSC at 50°C for an hour, 2xSSC at 50°C for 10 minutes, 2xSSC at RT for 10 minutes, 1xSSC at RT for 10 minutes, 0.5× SSC at RT for 10 minutes and 0.1xSSC at 50°C for 45 minutes. [score:2]
Other internal organs characterized to exhibit miR-205 expression appear morphologically normal in the non-surviving KOs, suggesting that miR-205 is not required for the gross development of these organ systems. [score:2]
It is well established that miR-205 actively regulates ZEB1 and ZEB2, factors that ensure proper maintenance of the epithelial fate [17] and it is tempting to speculate that miR-205 plays roles in proliferation or cell migration. [score:2]
miR-205 KOs also show signs of irregular skin development, evident by the appearance of dry skin and a much thinner skin layer (Fig 4A). [score:2]
The error bars shown are S. E. M. Tongue [T], nasal cavity [NC], whisker follicles [W], and salivary glands [Sm], oesophagus [O], trachea [Tr], stomach [S], glandular region of the stomach [G], non-glandular region of the stomach [NG] Analysis of E18.5 lung revealed a faint lacZ activity in the epithelial cells of bronchioles, suggestive of intermediate levels of miR-205 expression in bronchioles compared to the other lacZ -positive tissues (unpublished data). [score:2]
Improper regulation of miR-205 has been associated with increased metastasis in several tissue types, supporting a role of miR-205 in actively preventing EMT [28], [29], [30]. [score:2]
miR-205 knockout mice demonstrate postnatal lethality. [score:2]
While all organs exhibit grossly normal development in the miR-205 KOs, it is plausible that miR-205 is active in several processes essential for proper function of these organs such in basic epithelial function or epithelial regeneration and maintenance. [score:2]
In situ hybridization In situ hybdrization was done using LNA-probes against miR-205 (Exiqon) according to the manufacturer's directions with the following modifications: Post-hybridization washes: 2xSSC at 50°C for an hour, 2xSSC at 50°C for 10 minutes, 2xSSC at RT for 10 minutes, 1xSSC at RT for 10 minutes, 0.5× SSC at RT for 10 minutes and 0.1xSSC at 50°C for 45 minutes. [score:2]
LacZ Reporter provides high resolution and accurate readout of mature miR-205. [score:1]
That said, formally we cannot rule out an epigenetic or imprinted modifier of miR-205 activity. [score:1]
Further studies may reveal whether digestive disorders contribute to the observed lethality and a deeper understanding of miR-205 role(s) in homeostatic function. [score:1]
Images in C and E are higher magnifications of the dashed box shown in B and D. (F-G) miR-205 LNA in situs on stomach sections from wild type E14.5 embryos. [score:1]
Moreover, total RNA from selected E18.5 wild-type embryos tissues was subjected to qRT-PCR analysis for quantitating mature miR-205 levels (Fig 3H). [score:1]
In any case, the miR-205 KO animals are readily distinguished by weight between p4 and p6, with non-surviving KO animals weighing half that of their littermates by p7 (Fig 4C). [score:1]
The proximal stomach is composed of stratified squamous epithelium; consistent with the specificity of miR-205, lacZ activity was constrained to this non-glandular portion of the stomach (Fig 3D, E). [score:1]
Similarly, the current data hint that potential miR-205 genetic modifiers may be present, which could explain why the earlier report showed an earlier lethality [21]. [score:1]
miR-205 marks epithelial cell populations in internal organs. [score:1]
Expression in arbitrary units was calculated by (2 [15])×2 [−ΔCT] of miR-205 and sno202. [score:1]
LacZ reporter provides high-resolution localization of miR-205. [score:1]
Function -based analysis often benefits from a clean genetic background and a cleaner ablation of the miRNA, therefore miR-205 KO analysis was performed in C57BL/6 mice having only a single frt and loxP site footprint (Fig 1A). [score:1]
Partially penetrant lethality in miR-205 KO mice. [score:1]
In this study, the expression of miR-205 and constitutive KO phenotypes of a miR-205 mouse line was characterized. [score:1]
Moreover, it remains a possibility that miR-205 may play an important role in the maintenance and regeneration of hair follicles. [score:1]
In that study the miR-205 allele was zygotically replaced with a lacZ reporter in a mixed genetic background using a beta-Actin Cre transgene, yielding constitutive miR-205 KOs. [score:1]
For embryo staining, lacZ-miR-205 KO/+ embryos were dissected and fixed in 4% paraformaldehyde and 0.2% glutaraldehyde in PBS for either 1 or 4 hours depending on their age. [score:1]
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8
[+] score: 90
Together, these results suggest that miR-205-5p may specifically target 3′-UTR of VEGF mRNA to inhibit its translation in MSCs. [score:7]
Here, we showed that miR-205-5p is expressed in human MSCs, and inhibits VEGF protein translation through its association with VEGF mRNA. [score:7]
MiR-205-5p targets 3′-UTR of VEGF mRNA to inhibit its translation in MSCs. [score:6]
Very recently, VEGF has been found to be a target of miR-205-5p in glioma and miR-205-5p appears to be a glioma-specific tumor suppressor [20]. [score:5]
In the study that reported VEGF as a target of miR-205-5p in glioma [20], a different binding site on the 3′-UTR of VEGF mRNA from the current study was shown, suggesting the possible presence of different regulatory sites by miR-205-5p on the 3′-UTR of VEGF mRNA. [score:4]
Second, direct expression of VEGF may further increase the levels of miR-205-5p in MSCs as a negative feedback, which substantially reduces the systemic efficiency, or even leads to occurrence of ER stress. [score:4]
Here, we knocked down a highly expressed VEGF-antagonizing miRNA -miR-205-5p- in MSCs, which effectively increased VEGF and pro-angiogenic effects of MSCs. [score:4]
The role of miR-205-5p in carcinogenesis has been well documented, in which many targets of miR-205-5p have been defined in cancer cells [15– 19]. [score:3]
Expression of antisense of miR-205-5p (as-miR-205-5p) significantly increased levels of cellular and secreted VEGF by MSCs in vitro and in vivo. [score:3]
Very recently, VEGF has been found to be a target of miR-205-5p in glioma [20]. [score:3]
The results from the current study suggest that suppression of miR-205-5p in MSCs may be a promising strategy to increase their therapeutic potential in treating DF. [score:3]
The null or antisense for miR-205-5p (as-miR-205-5p) was cloned into a pCMV-DsRed-Express Vector (Catalog number: 632416; Clontech, Mountain View, CA, USA) backbone at the site between CMVp and red fluorescent protein (RFP). [score:3]
These data suggest that miR-205-5p may be a VEGF-regulatory miRNA in MSCs. [score:2]
However, a role of miR-205-5p in regulation of the therapeutic potential of MSCs in DF has not been reported. [score:2]
While as-miR-205-5p significantly increased luciferase activity of VEGF 3′-UTR wt, the presence of a mutation abolished this effect (Figure 3H). [score:2]
One week later, ulcers were generated in the right limp and the mice received intradermal transplantation of either mull-MSCs or as-miR-205-5p-MSCs at the site of ulcer. [score:1]
Depletion of miR-205-5p in grafted MSCs does not reverse diabetes. [score:1]
Next, we examined the effects of miR-205-5p depletion on wound healing from DF -associated ulcers. [score:1]
Transplantation of null-MSCs significantly increased vessel density, but the increases in vessel density by transplantation of as-miR-205-5p-MSCs appeared to be greater than transplantation of null-MSCs, shown by representative images (Figure 6B), and by quantification (Figure 6C). [score:1]
Depletion of miR-205-5p in grafted MSCs increases their therapeutic potential in DF. [score:1]
N = 5. Before we examined the effects of miR-205-5p-depletion in MSCs on their therapeutic potential in DF, we checked whether alteration of miR-205-5p levels may alter MSC property. [score:1]
We found that as-miR-205-5p-MSCs were able to be induced to differentiate into chondrocytes (Figure 4A), osteocytes (Figure 4B) and adipocytes (Figure 4C). [score:1]
We found that STZ -treated mice developed sustained hyperglycemia within 1 week, and grafting with either null-MSCs or as-miR-205-5p-MSCs did not reserve hyperglycemia (Figure 5B), which were supported by beta cell mass quantification (Figure 5C), demonstrated by representative immunostaining images for insulin (Figure 5D). [score:1]
Finally, we examined the effects of miR-205-5p-depletion in MSCs on their therapeutic potential in DF. [score:1]
We found that transfection with as-miR-205-5p reduced miR-205-5p levels in MSCs by about 80% (Figure 3D). [score:1]
However, the changes in VEGF levels by miR-205-5p appeared to be modest, and physiologically sound. [score:1]
Thus, depletion of miR-205-5p in MSCs increases their therapeutic potential in DF. [score:1]
Transplantation of null-MSCs improved wound healing, but transplantation of as-miR-205-5p-MSCs on wound healing appeared to have more pronounced effects than transplantation of null-MSCs (Figure 6A). [score:1]
Moreover, surface marker analysis for CD73, CD90, CD105, CD34, CD45 and HLA-DR in as-miR-205-5p-MSCs was consistent with an MSC phenotype (Figure 4D). [score:1]
Evidence of post-transcriptional control for VEGF by miR-205-5p in human MSCs. [score:1]
To confirm that this binding is functional, we transfected MSCs cells with plasmids carrying either as-miR-205-5p, or null as a control. [score:1]
Preservation of MSC properties in as-miR-205-5p -transfected MSCs. [score:1]
Although transfection by as-miR-205-5p did not alter VEGF mRNA in MSCs (Figure 3E), it significantly increased cellular VEGF protein (Figure 3F) and secreted VEGF protein (Figure 3G). [score:1]
MSCs depleted of miR-205-5p had increased therapeutic effects on DF in diabetic NOD/SCID mice. [score:1]
Group 1: untreated mice (UT: no STZ, no MSCs); group 2: STZ -treated mice (STZ; no MSCs); group 3: STZ+null-MSCs (STZ and transplanted with null-MSCs); group 4: STZ+as-miR-205-5p-MSCs (STZ and transplanted with as-miR-205-5p-MSCs). [score:1]
N = 5. Indeed, bioinformatics analyses showed that miR-205-5p bound to 3′-UTR of VEGF mRNA at 150th-157th base site (Figure 3A). [score:1]
One week later, ulcers were generated in the right limb and the mice received intradermal transplantation of either mull-MSCs or as-miR-205-5p-MSCs at the ulcer site. [score:1]
The effects of miR-205-5p-depletion in MSCs on their therapeutic potential in DF were examined. [score:1]
Figure 3(A) Bioinformatics prediction of binding site of miR-205-5p on 3′-UTR of VEGF mRNA (150th-157th base site). [score:1]
Preservation of MSC property by as-miR-205-5p -transfected MSCs. [score:1]
Moreover, the cellular VEGF protein (Figure 2G) and secreted VEGF protein (Figure 2H) were significantly increased only in miR-205-5p antisense (as-miR-205-5p) -transfected MSCs. [score:1]
Figure 5The effects of miR-205-5p-depletion in MSCs on their therapeutic potential in DF were examined. [score:1]
Indeed, bioinformatics analyses showed that miR-205-5p bound to 3′-UTR of VEGF mRNA at 150th-157th base site (Figure 3A). [score:1]
Evidence of presence of post-transcriptional control for VEGF by miR-205-5p in human MSCs. [score:1]
Figure 4(A) Differentiation of as-miR-205-5p-MSCs into chondrocytes by Alcian blue staining. [score:1]
N = 5. (A) Bioinformatics prediction of binding site of miR-205-5p on 3′-UTR of VEGF mRNA (150th-157th base site). [score:1]
Hence, transfection with as-miR-205-5p does not alter MSC properties. [score:1]
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9
[+] score: 82
The median log expression of the ten most deregulated miRNAs is given in Figure 4. The most up-regulated miRNA, mmu-mir-205-5p, was 135 times higher and the most down-regulated miRNA, mmu-mir-211-5p, was 35.7 times lower expressed in the curcumin -treated samples (Table 1). [score:12]
We demonstrate a growth -inhibitory effect of dietary curcumin and profound changes in miRNA expression with mmu-miR-205-5p being up-regulated most significantly. [score:8]
The ten most up-regulated miRNAs included mmu-miR-205-5p, mmu-miR-222-3p, mmu-miR-205-3p, mmu-miR-146b-5p, mmu-miR-21-5p, mmu-miR-21-3p, mmu-miR-221-3p, mmu-miR-140-3p, mmu-miR-142-5p, and mmu-miR-140-5p and the ten most down-regulated miRNAs comprised mmu-miR-211-5p, mmu-miR-3096-5p, mmu-miR-711, mmu-miR-466h-5p, mmu-miR-130b-3p, mmu-miR-3082-5p, mmu-miR-1199-5p, mmu-miR-669b-5p, mmu-miR-1187, and mmu-miR-1224-5p (Table 1). [score:7]
Up-regulation of mmu-miR-205-5p and-3p has been shown to reverse epithelial-to-mesenchymal transition in various tumors with E-cadherin as a central target [42], [43]. [score:6]
To investigate the expression of putative targets of mmu-miR-205-5p, which was identified to be the most up-regulated miRNA under curcumin treatment, the whole protein fractions were purified from the organic phase of the phenol/guanidine -based RNA-isolation of four randomly chosen curcumin -treated and four control tumors. [score:6]
Based on our in silico analyses, we selected anti-apoptotic Bcl-2 and the transcription factor E2F1 for PCNA to validate some of the predicted targets of mmu-miR-205-5p, which was the most highly regulated miRNA by curcumin treatment. [score:4]
This indicates that the expression of this proliferation marker may be regulated by other miRNAs than mmu-miR-205-5p or by other transcription factors than E2F1. [score:4]
The top ten miRNAs being significantly up-regulated by curcumin treatment comprised mmu-miR-205-5p (135-fold), mmu-miR-205-3p (9-fold) and mmu-miR-142-5p (6-fold). [score:4]
In conclusion, we demonstrate for the first time a clear impact of dietary curcumin on the miRNA profile in murine melanoma with mmu-miR-205-5p being up-regulated most extensively. [score:4]
Taken together, these results indicate that the curcumin-regulated miRNAs mmu-miR-205-5p, mmu-miR-205-3p, mmu-miR-142-5p and mmu-miR-130b-3p represent promising targets as well as markers to determine the aggressiveness and metastatic activity of malignant tumors. [score:4]
To investigate whether the curcumin -induced expression pattern of the key miRNAs identified in the in vivo experiments is also transferable to other melanoma cell lines, murine B78H1 cells as well as human SK-MEL-28 (ATCC® HTB-72™) and MeWo cells (ATCC® HTB-65™) were treated with 20 µM curcumin or vehicle (0.1% DMSO; control) at 37°C and 5% CO [2] for 48 h. Subsequently, the cells were harvested and the expression of mmu-miR-205-5p, mmu-miR-205-3p (or hsa-miR-205-3p for human cells), mmu-miR-142-5p and mmu-miR-130b-3p was analyzed by qRT-PCR, as described above. [score:3]
For the validation of the miRNA microarray results, qRT-PCR was performed to analyze the expression of the four selected miRNAs mmu-miR-205-5p, mmu-miR-205-3p, mmu-miR-142-5p and mmu-miR-130b-3p using miScript PCR System (Qiagen). [score:3]
Hsa-miR-205 was found to be 100 times down-regulated in human metastatic melanoma compared to non-metastatic ones [38]. [score:3]
The expression levels of mmu-miR-205-5p, mmu-miR-205-3p, mmu-miR-142-5p and mmu-miR-130b-3p, which have previously been described in the literature as miRNAs with potential anti-cancer properties [37], [38], were confirmed by qRT-PCR (Figure 2). [score:3]
Based on the current literature and our in silico analyses, predicted targets of mmu-miR-205-5p include E2F1, E2F3, E2F5, Bcl-2, CD31, hypoxia-inducible transcription factor (HIF)-1α, and VEGF [49], [50]. [score:3]
0081122.g002 Figure 2 The diagrams display bar charts on the fold expression (compared to control) of mmu-miR-205-5p, mmu-miR-205-3p, mmu-miR-142-5p and mmu-miR-130b-3p in curcumin -treated B78H1 melanoma, as assessed by miRNA array (grey bars) and qRT-PCR (black bars). [score:2]
The diagram displays bar charts on the fold expression (compared to vehicle -treated control cells) of mmu-miR-205-5p, mmu-miR-205-3p, mmu-miR-142-5p and mmu-miR-130b-3p of curcumin -treated murine B78H1 (white bars), human SK-MEL-28 (grey bars) and human MeWo melanoma cells (black bars), as assessed by qRT-PCR. [score:2]
0081122.g003 Figure 3 The diagram displays bar charts on the fold expression (compared to vehicle -treated control cells) of mmu-miR-205-5p, mmu-miR-205-3p, mmu-miR-142-5p and mmu-miR-130b-3p of curcumin -treated murine B78H1 (white bars), human SK-MEL-28 (grey bars) and human MeWo melanoma cells (black bars), as assessed by qRT-PCR. [score:2]
The diagrams display bar charts on the fold expression (compared to control) of mmu-miR-205-5p, mmu-miR-205-3p, mmu-miR-142-5p and mmu-miR-130b-3p in curcumin -treated B78H1 melanoma, as assessed by miRNA array (grey bars) and qRT-PCR (black bars). [score:2]
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[+] score: 81
Metformin counteracts PKM2 inactivation and therefore i) impairs the formation of the HIF-1α/DEC1/PKM2 trimeric complex (Figure 5E), ii) downregulates CAF -induced miR205 expression (Figure 5F), iii) inhibits CAF -induced EMT promotion (Figure 5G) and subsequent cells invasive ability (Figure 5H). [score:8]
Comparable results were obtained in DU145 cells, confirming the ability of metformin to inhibit PKM2 nuclear translocation and CAF -induced inhibition of miR205 expression, thereby impairing EMT execution (Supplementary Figure S6A–S6D). [score:7]
The absence of the PKM2/HIF-1α/DEC1 complex does not allow PC3 cancer cells to downregulate miR205 expression once treated with CAFs CM (Supplementary Figure S4B). [score:6]
In keeping with its role of transcriptional repressor, de novo expression of DEC1 and the formation of the trimeric complex DEC1/PKM2/HIF-1α is mandatory for allowing miR205 downregulation after CAFs conditioning (Figure 4F) and for EMT induction (Figure 4G). [score:6]
F. PC3 cells were treated as in E. qRT-PCR analysis of miR-205 expression is reported as log [10]-transformed relative expression with respect to HPF-CM-PC3 treated cells. [score:5]
As already observed in PC3 cells, DASA-58 administration abrogates the CAF -induced miR205 downregulation in DU145 cells (Supplementary Figure S5B), thereby interfering with the EMT execution and the pro-invasive input elicited by CAFs (Supplementary Figure S5C–S5E). [score:4]
F. qRT-PCR analysis of miR-205 expression is shown as log [10]-transformed relative expression compared to HPF-CM-PC3 treated cells. [score:4]
Recently, microRNA 205 (miR205) has been demonstrated to be a negative regulator of EMT and its expression inversely correlated with tumor malignancy [10, 11]. [score:4]
b. The pro-oxidant environment induced by CAFs drives the oxidation and the Src -mediated tyrosine phosphorylation of PKM2, promoting its nuclear association with HIF-1α/DEC1, downregulation of miR205 and EMT execution. [score:4]
Indeed, miR205 downregulation induced by CAFs exposure is completely counteracted by DASA-58 treatment (Figure 2C). [score:4]
Quantification of miR-205 expression levels was assessed by quantitative reverse transcriptase PCR (qRT-PCR). [score:3]
This trimeric complex drives miR205 transcriptional suppression leading to EMT accomplishment and metabolic conversion to OXPHOS of PCa cells. [score:3]
Indeed, PCa cells decrease miR205 expression upon CAFs contact, allowing de-repression of ZEB1/2 transcription factors and therefore promoting EMT [11]. [score:3]
Moreover, the impairment of PKM2/HIF-1α association significantly affects the expression of miR205, a critical miRNA driving CAF -mediated EMT in PCa cells [11] (Figure 2C). [score:3]
C. miR-205 expression levels were quantified by qRT-PCR. [score:3]
To clarify the molecular mechanism that control miR205 expression, we evaluated whether other transcriptional regulators could be recruited at the PKM2/HIF-1α complex. [score:2]
Once in the nucleus, PKM2 can associate with HIF-1α and the transcriptional repressor DEC1, thus culminating in miR205 regulation, EMT execution and enhancement of invasiveness (Figure 7D a,b). [score:2]
Interestingly, in silico analysis of the miR205 promoter region by Genomatix (www. [score:1]
Three human MIR205 [NC_000001 (+) 209602165 – 209605890] files generated by Gene2Promoter analysis (GXP_144577, GXP_144578, GXP_4402679) were used to determine sites of DEC1 binding using Mat Inspector (www. [score:1]
These modifications are mandatory for PKM2 translocation into the nucleus, association with HIF-1α and DEC1 and induction of miR205 -dependent EMT. [score:1]
DEC1 is recruited by the PKM2/HIF-1α complex upon CAFs exposure, granting for miR205 transcriptional repression and EMT execution. [score:1]
A. Schematic representation of putative DEC1 binding site within the miR205 promoter region identified using Genomatix Suite. [score:1]
To further support the transcriptional repressive role of DEC1 in our mo del, we investigated the effect of the redox insensitive Src mutants (Src C245A and Src C487A) on DEC1/PKM2 association and the consequential modulation of miR205 expression. [score:1]
In silico binding site analysisThree human MIR205 [NC_000001 (+) 209602165 – 209605890] files generated by Gene2Promoter analysis (GXP_144577, GXP_144578, GXP_4402679) were used to determine sites of DEC1 binding using Mat Inspector (www. [score:1]
The reverse transcription reaction of 1 μg of total RNA was carried on using miScript II RT kit and the quantification of miR205 expression level was assessed by Real Time PCR using miScript SYBR Green PCR kit and miScript Primer Assay-HsmiR-205. [score:1]
Figure 4 A. Schematic representation of putative DEC1 binding site within the miR205 promoter region identified using Genomatix Suite. [score:1]
HPF -treated PC3 cells also maintain high levels of miR205, thus allowing the stabilization E-cadherin -mediated epithelial features. [score:1]
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11
[+] score: 53
For example, the targets of the mir-135 family, a family that was up-regulated in the vestibule, were enriched in a set of proteins down-regulated in this tissue; and the targets of mir-205, a miRNA that exhibited a higher expression in the cochlea, were depleted in a set of proteins also up-regulated in the cochlea. [score:16]
Thus, for six miRNA families – mir-135, mir-205, mir-142-3p, mir-15/16, mir-218 and mir-24 - we obtained evidence for their functional relevance in the inner ear on two levels: (a) the miRNAs were differentially expressed between the two tissues; and (b) their predicted targets were differentially expressed in a manner consistent with the currently accepted mo del of miRNA regulation. [score:8]
For further study, we selected miR-135b and miR-205, for which miRNA target enrichment or depletion, respectively, were detected only at the protein expression level and therefore would not have been identified by analyzing transcript data alone. [score:5]
Almost all cochlear cells, including those of the modiolus, were found to express miR-205. [score:3]
Some of the cells in the auditory apparatus did not show miR-205 expression, including many of the cells facing the scala media. [score:3]
Expression patterns for miR-135b (C) and miR-205 (D) were consistent with the miRNA array analysis. [score:3]
As expected from the miRNA microarray data, miR-205 expression was mainly limited to the cochlea. [score:3]
The spatial expression pattern of miR-135b and miR-205 in the inner ear of P0 mice was determined using in situ hybridization (ISH; Figure 3), and suggested differences in miRNA function across the cochlea and vestibular organs. [score:3]
For two miRNAs, miR-135b and miR-205, we localized their cell specific expression in the inner ear using in situ hybridization. [score:3]
Distinct spatial expression patterns of miR-135b and miR-205 in the newborn mouse inner ear. [score:3]
We found miR-205 to be expressed in cells of the spiral ligament, part of the Reissner's membrane, basilar membrane and apical surface of the spiral limbus. [score:3]
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[+] score: 47
At 30 weeks of age, the expression of miR-216 (p-value = 0.016), miR-217 (p-value = 0.0078), miR-150 (p-value =0.023), Let-7b (p-value = 0.031,) and miR-96 were significantly downregulated, whereas the expression of miR-146b (p-value = 0.0078), miR-205, (p-value - 0.0078), miR-21, miR-195 (p-value = 0.031), and miR-34c (p-value = 0.063) were significantly upregulated in KC animals compared to control animals (Figure 2B). [score:10]
At 40 weeks of age, the expression of miR-216, miR-217, miR-223, miR-141, miR-483-3p (p-value = 0.031), miR-195, Let-7b (p-value = 0.063) and miR-96 were significantly downregulated; on the other hand, the expression of miR-21, miR-205, miR-146b (p-value = 0.031), and miR-34c (p-value = 0.063) were upregulated in KC mice compared to the control animals (Figure 2C). [score:10]
We have shown that in tumor samples compared to normal samples, the majority of miRNAs (miR-216, miR-217, miR-100, miR-345, miR-141, miR-483-3p, miR-26b, miR-150, Let-7b, Let-195 and miR-96) were downregulated, and few were upregulated (miR-146b, miR-205, miR-31, miR-192, miR-194 21, miR-379, miR-431, miR-541, and miR-199b). [score:6]
The analysis for the KC animals compared to controls revealed that miR-150, miR-494, miR-138, miR-148a*, miR-216a, and miR-217 (p-value = 0.01) were significantly downregulated (Table 1), whereas, miR-146b, miR-205, miR-31, miR-192, and miR-21 (p-value = 0.01) were significantly upregulated (Table 2). [score:6]
The expressions of miR-216 and miR-217 were also progressively reduced in KC mice, but the expressions of miR-21, miR-205, miR-146b, miR-34c, and miR-223 progressively increased (Figure 1A, 2A– 2D). [score:5]
Rieu et al. also reported in the KC animals, progressive increases in miR-21 and miR-205 expression from PanIN lesions to full-blown PDAC, with strongest expression of miR-21 in precursor lesions with phenotypic changes in the ducts [69]. [score:5]
Similarly, we also observed upregulation of miR-21 and miR-205 in human PC samples compared to cancer- adjacent normal tissue (Figure 3E). [score:3]
Several reports have also shown elevated expression of miR-21 and miR-205 in a panel of PC cell lines and tissues compared to the normal controls [40– 42, 50, 55, 60, 65– 68]. [score:2]
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[+] score: 40
Other miRNAs from this paper: hsa-let-7c, hsa-let-7d, hsa-mir-16-1, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-28, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-99a, hsa-mir-101-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-99a, mmu-mir-101a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-128-1, mmu-mir-9-2, mmu-mir-142a, mmu-mir-144, mmu-mir-145a, mmu-mir-151, mmu-mir-152, mmu-mir-185, mmu-mir-186, mmu-mir-24-1, mmu-mir-203, hsa-mir-148a, hsa-mir-34a, hsa-mir-203a, hsa-mir-205, hsa-mir-210, hsa-mir-221, mmu-mir-301a, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-142, hsa-mir-144, hsa-mir-145, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-185, hsa-mir-186, mmu-mir-148a, mmu-mir-200a, mmu-let-7c-1, mmu-let-7c-2, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-21a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-34a, mmu-mir-148b, mmu-mir-339, mmu-mir-101b, mmu-mir-28a, mmu-mir-210, mmu-mir-221, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, mmu-mir-128-2, hsa-mir-128-2, hsa-mir-200a, hsa-mir-101-2, hsa-mir-301a, hsa-mir-151a, hsa-mir-148b, hsa-mir-339, hsa-mir-335, mmu-mir-335, hsa-mir-449a, mmu-mir-449a, hsa-mir-450a-1, mmu-mir-450a-1, hsa-mir-486-1, hsa-mir-146b, hsa-mir-450a-2, hsa-mir-503, mmu-mir-486a, mmu-mir-542, mmu-mir-450a-2, mmu-mir-503, hsa-mir-542, hsa-mir-151b, mmu-mir-301b, mmu-mir-146b, mmu-mir-708, hsa-mir-708, hsa-mir-301b, hsa-mir-1246, hsa-mir-1277, hsa-mir-1307, hsa-mir-2115, mmu-mir-486b, mmu-mir-28c, mmu-mir-101c, mmu-mir-28b, hsa-mir-203b, hsa-mir-5680, hsa-mir-5681a, mmu-mir-145b, mmu-mir-21b, mmu-mir-21c, hsa-mir-486-2, mmu-mir-126b, mmu-mir-142b, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
The expression of miR-205 was also reported to be down-regulated in prostate cancer cells, and ectopically expressed miR-205 showed a tumor-suppressive effect, including reduction of cell migration and tissue invasion [36]. [score:10]
Of the down-regulated miRNAs a number have been reported to be down-regulated in prostate cancer relative to benign prostate tissues, i. e. miR-16 [23]– [25], miR-24 [26]– [28], miR-29a [26], miR-145 [23], [24], [27], [29], [30], and miR-205 [24], [31], [32]. [score:7]
[Epub ahead of print] 36 Gan dellini P Folini M Longoni N Pennati M Binda M 2009 miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon. [score:6]
The down-regulation of miR-16 [25], miR-34a [33], miR-126* [34], miR-145 [35] and miR-205 [36] correlated with the development of prostate cancer metastasis. [score:5]
Thus some of the miRNAs have already been linked to this phenomenon, in particular down-regulated miRNAs such as miR-16, miR-34a, miR-126*, miR-145 and miR-205, supporting the validity of our analytical approach. [score:4]
A number of these miRNAs (21/104) have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e. g., miR-16, miR-34a, miR-126*, miR-145, miR-205) have been linked to prostate cancer metastasis, supporting the validity of the analytical approach. [score:4]
Of the down-regulated miRNAs, 24 miRNAs showed a >5-fold decrease, including four miRNAs, i. e. miR-205, miR-503, miR-708 and miR-2115*, which were undetectable in the metastatic line. [score:4]
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[+] score: 38
A hypothetical mo del of age -dependent miRNAs regulating LCs development and function is shown in Figure 6. Table 1 miRNAs in aging putative targets function in LC reference miR709↑ RANK LC development and homeostasis↓ 49 IRF8 LC development and homeostasis↓ 29 AhR impair LC maturation 33 miR449↑ TGFβRII LC development and homeostasis↓ 32, 46 RunX3 LC development and homeostasis↓ 30 CSF1R LC development and survival↓ 35 miR9↑ TGFβRII LC development and turnover↓ 32, 46 RunX3 LC development and homeostasis↓ 30 RANK LC development and homeostasis↓ 49 miR10a↓ Gfi1 LC development and homeostasis↓ 28 miR200c↓ C/EBP LC differentiation↓ 31 Langerin LC antigen uptake ↑ 22, 23 Gfi1 LC development and homeostasis↓ 28 miR744↓ TGFβI inhibit LC maturation 32, 46 miR20b↓ RANKL inhibit LC maturation 34 miR205↓ C/EBP LC differentiation↓ 31 (A) LCs were isolated using AutoMACS with anti-MHCII-PE and anti-PE microbeadsfollowed by a cell sorter. [score:19]
A hypothetical mo del of age -dependent miRNAs regulating LCs development and function is shown in Figure 6. Table 1 miRNAs in aging putative targets function in LC reference miR709↑ RANK LC development and homeostasis↓ 49 IRF8 LC development and homeostasis↓ 29 AhR impair LC maturation 33 miR449↑ TGFβRII LC development and homeostasis↓ 32, 46 RunX3 LC development and homeostasis↓ 30 CSF1R LC development and survival↓ 35 miR9↑ TGFβRII LC development and turnover↓ 32, 46 RunX3 LC development and homeostasis↓ 30 RANK LC development and homeostasis↓ 49 miR10a↓ Gfi1 LC development and homeostasis↓ 28 miR200c↓ C/EBP LC differentiation↓ 31 Langerin LC antigen uptake ↑ 22, 23 Gfi1 LC development and homeostasis↓ 28 miR744↓ TGFβI inhibit LC maturation 32, 46 miR20b↓ RANKL inhibit LC maturation 34 miR205↓ C/EBP LC differentiation↓ 31 The density of LCs in the epidermis is known to decrease with age in mice [21]. [score:19]
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[+] score: 33
Results from our analyses reveal significant inhibition of miRs-182 and 205 in the VA of obese NZ10 mice and increased expression of miR-205 in 3T3-L1 during adipogenesis (Figure 3e) [17]. [score:5]
MiR-205 has been shown to target ErbB3 in cancer cells and it is known that ErbB3 is expressed in 3T3-L1 cells [19, 20]. [score:4]
MiR-205 was unique insofar as its expression was significantly elevated at all-time points during adipogenesis in parallel with expression of the PPARγ gene (Figures 3e,3d). [score:4]
This revealed that suppression of miRNA-205 alone correlated selectively with increased cell proliferation and lipid formation of adipocytes. [score:3]
These results show a significant increase in preadipocyte proliferation by inhibition of miR-205 (Figure 4C). [score:3]
In addition to this upon adding the adipogenesis induction medium to 3T3-L1 cells after miRNA modulation and staining for lipid formation at Day 3, we found significantly increased oil red O staining in the miR-205 inhibited group (Figure 4A, 4B). [score:3]
We hypothesize that miR-205 targets ErbB3 in adipocytes and enhances proliferation; this in turn enhances adipogenesis and lipid production in cultured 3T3L-1 cells after induction to differentiate. [score:3]
We show for the first time that miR-205 inhibition in 3T3-L1 preadipocytes increases cell proliferation and lipid accumulation after adipogenic induction. [score:3]
Preadipocytes were transfected with pre or anti-miR-205 oligos (Life Technologies, Grand Island, NY) according to manufacturer’s instructions. [score:1]
To this end we modified miR-205 expression in 3T3-L1 preadipocytes with either pre or anti-miRs and evaluated cell cycle proliferation. [score:1]
Here we report that miRNA-205 is selectively implicated in adipocyte division and lipid accumulation in vitro and in vivo. [score:1]
Because members of miR-200 family and miR-205 showed significant inhibition in the VA of obese mice, we chose to evaluate whether any of these miRNAs are implicated in adipogenesis. [score:1]
Preadipocytes were transfected with pre (10 μM) or anti-miR-205 (10 μM) in 6 well plates. [score:1]
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[+] score: 30
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-18a, hsa-mir-22, hsa-mir-29a, hsa-mir-30a, hsa-mir-93, hsa-mir-100, 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-30b, mmu-mir-124-3, mmu-mir-126a, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-146a, mmu-mir-200b, mmu-mir-203, mmu-mir-204, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10a, hsa-mir-34a, hsa-mir-203a, hsa-mir-204, hsa-mir-205, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-221, hsa-mir-222, hsa-mir-200b, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, 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-133a-1, hsa-mir-133a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-146a, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-148a, 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-18a, mmu-mir-22, mmu-mir-29a, mmu-mir-29c, mmu-mir-93, mmu-mir-34a, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-10a, mmu-mir-100, mmu-mir-200c, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-221, mmu-mir-222, mmu-mir-29b-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-375, mmu-mir-375, hsa-mir-335, mmu-mir-335, mmu-mir-133a-2, hsa-mir-424, hsa-mir-193b, hsa-mir-512-1, hsa-mir-512-2, hsa-mir-515-1, hsa-mir-515-2, hsa-mir-518f, hsa-mir-518b, hsa-mir-517a, hsa-mir-519d, hsa-mir-516b-2, hsa-mir-516b-1, hsa-mir-517c, hsa-mir-519a-1, hsa-mir-516a-1, hsa-mir-516a-2, hsa-mir-519a-2, hsa-mir-503, mmu-mir-503, hsa-mir-642a, mmu-mir-190b, mmu-mir-193b, hsa-mir-190b, mmu-mir-1b, hsa-mir-203b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-126b, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
Top conserved miRNAs in the MaSC/basal population include miR-204 (may target ERα), miR-221/222 (targets ERα and c-Kit) [37, 38], and miR-205 (targets Pten and Bcl-2) [39, 40]. [score:7]
Gregory PA Bert AG Paterson EL Barry SC Tsykin A Farshid G The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1Nat Cell Biol. [score:4]
Verdoodt B Neid M Vogt M Kuhn V Liffers ST Palisaar RJ MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancerInt J Oncol. [score:4]
Conversely, miR-146a, miR-221/222, and miR-205, which have been shown to regulate genes expressed in the ductal and alveolar luminal lineages (e. g., Brca1, Gata3, c-kit and Elf5), were restricted to the MaSC/basal population. [score:4]
For example, miR-205 is one the most significantly downregulated miRNAs in human breast cancer relative to normal tissue [22]. [score:4]
In the mouse mammary epithelial cell line, Comma-Dβ [19], the expression of miR-205 and miR-22 but not let-7 and miR-93 was linked to progenitor-like properties, while miR-200c appears to function within the basal cell compartment of normal breast tissue [20]. [score:3]
More specifically, the expression of some miRNAs has been linked to histopathological features such as HER2/ neu or ER/PR status (miR-30), metastasis (miR-126 and miR-335) and the EMT (miR-205 and miR-200 family) [43, 76– 79]. [score:3]
Conversely, we observed derepression of luminal-specific miR-34a, miR-205 and miR-222 in the MaSC/basal subset of Ezh2 -deficient glands (data not shown). [score:1]
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[+] score: 29
Specifically, two miRNAs (miR-18a-5p and miR-574-3p) were upregulated in the Mn [2+] -induced NPA mo del, while let-7e-5p was downregulated and miR-205-5p was upregulated in the chlorpromazine -induced NPA mo del. [score:10]
In the lupus-like disease produced by chlorpromazine -induced NPA, let-7e-5p and miR-205-5p were downregulated and upregulated, respectively. [score:9]
Among them, let-7e-5p and miR-205-5p, found only in the mo del produced with chlorpromazine -induced NPA, are known to enhance TLR4 expression (let-7e-5p) [21], provoke ERBB3 downregulation, and decrease apoptosis (miR-205-5p) [47]. [score:6]
The remaining six deregulated miRNAs: let-7e-5p, miR-18a-5p, miR-23b-3p, miR-205-5p, miR-207, and miR-574-3p, which are specific to each of our murine lupus-like mo dels, highlight some differences between them, but also show roles on inflammation and immune disease. [score:4]
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[+] score: 29
Other miRNAs from this paper: mmu-mir-200b, mmu-mir-203, mmu-mir-200a, mmu-mir-200c
It has been reported that the EMT-inducing transcription factors, which suppress the CDH1 expression, are negatively regulated by the miRNAs (miR-200 family, miR-203, and miR-205, etc. ) [score:6]
In our study, elevated expression of miR-203 and miR-205 was detected in the two lines of RICs, suggesting that they might act as tumor suppressors in addition to MET inducers by repressing EMT -associated genes. [score:5]
With regard to miR-205, the roles were identified as a tumor suppressor by inhibiting proliferation and invasion, or as an oncogene by facilitating tumor initiation and proliferation in various kinds of tumors [41]. [score:5]
The HOC313 RICs showed increased levels of miR-200 family members (miR-200a, -200b, -200c, -141, and -429), miR-203, and miR-205 (Fig 3G), which could down-regulate the SNAI and ZEB families [15– 17]. [score:4]
In accordance with this observation, significant up-regulation of miR-200 family, (miR-200a, -200b, -200c, -141, and -429), miR-203, and miR205 was detected in the RICs from HOC313 cells. [score:4]
It was reported the miR-205 expression was abundantly found in cutaneous SCC [42], although other studies showed no significant correlation between miR-205 and metastasis in oral SCC [43]. [score:3]
The OSC-19 RICs showed increased levels of miR-203 and miR-205, although the miR-200 family members were not altered (Fig 4I). [score:1]
Insights into the diverse roles of miR-205 in human cancers. [score:1]
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[+] score: 29
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-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, hsa-mir-206, 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
Out of these 25 miRNAs, 18 miRNAs were differentially expressed in a consistent manner between the 2 groups (Figure 4A, highlighted); 8 miRNAs were downregulated in both groups (miR-16, miR-200, miR-205, miR-3064, miR-379, miR-431, miR-485 and miR-491) and 10 miRNAs were upregulated in both groups (miR-194, miR-1894, miR-211, miR-3072, miR- 3077, miR-4436, miR-5128, miR-669a, miR-669c and miR-6967). [score:9]
The study revealed downregulation of miR-205, miR-27, miR-31, and miR-29 in the cbs [+/–] retinas, these miRNAs were also reported to be downregulated in vitreous [68] and plasma of AMD patients [69]. [score:7]
The study revealed downregulation of miR-205, miR-27, miR-31, and miR-29 in the cbs [+/–] retinas. [score:4]
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]
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]
Hcy also induces alteration of miRNAs related to tight junctions signaling such as miR-128, miR-132, miR-133, miR-195, miR-3473, miR-19, miR-200, miR-205, miR-214, miR-217, miR-23, miR-26, miR-29, miR-30, miR-31 AND miR-690. [score:1]
Other miRNAs were linked to the hypoxia signaling pathway, for instance, miR-205, miR-214, miR-217, miR-27, miR-29, miR-30 and miR-31. [score:1]
miR-205, miR-27, miR-29 and miR-31 were significantly changed in our cbs [+/–] retina microarray and were also reported to be involved in AMD. [score:1]
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[+] score: 28
[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]
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]
For example, it is possible that repression of Brca1 in the epithelial compartment of the mammary gland causes upregulation of miR-135b, miR-155 and miR-205 in nonepithelial cells of the mammary gland. [score:4]
In contrast to the analysis of Brca1 -deficient mammary glands (Figure 1a), upregulation of miR-135b, miR-155 and miR-205 was not observed in HC11 cells in which Brca1 levels have been repressed using siRNA (Figure 1c). [score:4]
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]
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21
[+] score: 25
PJ up-regulates genes involved in cell adhesion such as E-cadherin, intercellular adhesion molecule 1 (ICAM1) and myristoylated alanine-rich protein kinase C (MARCKS) and down-regulates genes involved in cell migration such as type I collagen, tenascin C and chimerin 1. In addition, anti-invasive microRNAs such as miR-335 (predicted targets include COL1A1, TNC, SOX4), miR-205 (predicted targets include CHN1, PRKCE), miR-200 (predicted targets include ZEB1, ZEB2), and miR-126 (predicted targets include SLC45A3), are up-regulated, whereas pro-invasive microRNA such as miR-21 (predicted targets include MARCKS, PDCD4, TPM1) and miR-373 (predicted targets include CD44), are down-regulated. [score:25]
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[+] score: 24
At 14 weeks from injection and in the presence of tumor, miR-205-5p was significantly downregulated and miR-214 and miR-574-3p were upregulated. [score:7]
Three of the four miRNAs (miR-205-5p-5p, miR-214, and miR-335-5p) were validated in an independent set of diseased and wild-type mice to be statistically significant (P < 0.05) using a two-sample, two-tailed Student’s t-test comparing the 2 [−ΔCq] values of the two groups MicroRNA-574-3p was not statistically significant in final statistical analysis, but was included in simultaneous studies based on preliminary results (P =  0.15) (Fig. 1). [score:3]
Our studies revealed plasma miR-205-5p was downregulated in GEMM mice with OS compared to wild-type littermate controls, whereas levels of miR-214 and miR-335-5p were significantly higher in GEMM mice. [score:3]
The levels of miR-205-5p, miR-574-3p, and miR-214 were significant from baseline at the time of tumor development (14 week time point). [score:2]
Furthermore, recent evidence suggests that miR-205-5p is highly specific to epithelium, which may explain the results in the DOX experiments which do not show a significant decrease in the disease state compared to baseline likely due to the method of blood sampling. [score:2]
qPCR analysis of miR-205-5p, -574-3p, -214 and -335-5p upon randomization and at time of sacrifice in placebo treated and DOX treated. [score:1]
Therefore, we monitored the levels of miR-205-5p, miR-214, miR-335-5p, and miR-574-3p prior to and serially after transplantation of OS cells. [score:1]
Four miRNAs (miR-205-5p-5p, miR-214, miR-335-5p, and miR-574-3p) were chosen as candidate miRNAs based on reports in published literature, the presence of a conserved known human homologue, and the fold change in the global qPCR analysis. [score:1]
The ΔCq cut-points were 8.34 for miR-205-5p, 10.31 for miR-214, 9.78 for miR-335-5p and 6.08 for miR-574-3p. [score:1]
While our study is the first report of plasma miR-205-5p, miR-214, miR-335-5p, and miR-574-3p to be used as biomarkers, the literature supports that each of these miRNAs may have an important biologic function in OS. [score:1]
Areas under the curve (AUCs) were 0.70 (95% CI 0.576–0.827), 0.80 (95% CI 0.699–0.909), 0.78 (95% CI 0.661–0.898), and 0.88 (95% CI 0.794–0.957) for miR-205-5p, miR-214, miR-335-5p, and miR-574-3p, respectively. [score:1]
As shown in Figure 5A, the areas under the curves (AUCs) were 0.70 (95% CI 0.576–0.827), 0.8 0(95% CI 0.699–0.909), 0.78 (95% CI 0.661–0.898), and 0.88 (95% CI 0.794–0.957) for miR-205-5p, miR-214, miR-335-5p, and miR-574-3p, respectively. [score:1]
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[+] score: 21
Within the epithelial compartment, cell type-specific expression was demonstrated for let-7 and miR-205, which were predominantly expressed in luminal and basal cells, respectively, confirming previous reports of their expression in human luminal and basal breast epithelium [40]. [score:7]
miR-205 (cluster 3) was strongly expressed in the basal epithelium until the mature virgin stage, showing increased expression in both luminal and basal epithelium during pregnancy and in late involution. [score:5]
On the other hand, miR-22 and miR-205, which were reported to be highly expressed in mammary progenitor cells [38], seemed to be enriched during gestation and again during late involution. [score:3]
Higher-magnification images of in-situ hybridisation for miRNAs let-7b, miR-205, and miR-206, showing higher expression in the epithelial compared to the stromal cell compartment, and specificity for the luminal and basal epithelial cell layers for let-7b and miR-205, respectively. [score:2]
Figure 4 In-situ hybridisation for miRNAs let-7b (cluster 1), miR-205 (cluster 3), and miR-206 (cluster 6) shows higher expression in the epithelial compared to the stromal cell compartment. [score:2]
Two miRNAs, namely let-7b and miR-205, showed specificity for the luminal and basal epithelial cell layers, respectively, during juvenile, puberty, and mature virgin stages. [score:1]
let-7b and miR-205 show specificity for the luminal and basal epithelial cell layers, respectively. [score:1]
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24
[+] score: 20
We observed a significant reduction in the expression of miR21, miR34a, miR200c, miR203 and miR19a, whereas miR200a, miR200b and miR205 displayed increased expression in HuΔNp63α -expressing 940 cells (Fig. 2I). [score:7]
Importantly, the reduction of miR21, miR19a and miR203, and the increased expression of miR200a, miR200b and miR205 are compatible with a possible reduction in the metastatic potential of 940 cells upon ectopic expression of huΔNp63α, and may explain the indirect regulation of EMT-mediating transcription factors described above. [score:7]
In the present study we show that the experimental deregulation of p63 levels promoted altered expression of various miRNA previously involved in EMT and tumor metastasis, including miR-21, miR-34a, miR-200a, miR-200b, miR-203, miR19a and miR205. [score:4]
These include miR21, miR200 family, miR34 family, miR130a, miR203, miR19a and miR205. [score:1]
Of note, several of these miRNAs have been identified in ChIP-seq experiments and display binding sites for p53 (miR-21, miR34a), p63 (miR-200a, miR-200b) or both (miR-205) [20, 60]. [score:1]
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25
[+] score: 20
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-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, hsa-mir-206, 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 example, the cluster of miR-512-3p, miR-205, and the miR-302 family illustrated on the heat map demonstrates high expression in undifferentiated ES and early neural progenitor stages, downregulation during the glial restricted and early OP transitions, but then additional high expression during mid to late OP development. [score:9]
Additionally, miR-205 showed a ∼9.2-fold downregulation during the OP3 to OL transition, which contains a conserved 8mer complementary site within the Cldn11 3′-UTR. [score:4]
During the final stage transition, miR-205 showed significant downregulation. [score:4]
As such, the decrease of miR-205 may be partially responsible for the increased expression of Cldn11 at this stage. [score:3]
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26
[+] score: 18
We also found seven deregulated miRNAs to target E2F1 transcript, especially emphasizing the importance of miR-203a and miR-205-5p that were strongly down-regulated. [score:7]
miR-205-5p is known to be down-regulated in melanoma and its expression inversely correlated with that of E2F1 [48]. [score:6]
Our microRNA analysis also revealed a consistent deregulation of seven miRNAs in T-LBLs, miR-203a and miR-205-5p being the most representative downregulated microRNAs (Figs. 5 and 6). [score:5]
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27
[+] score: 17
Dot plots show the expression levels of miR-146a, miR-193b, miR-205, miR-215, miR-467a, miR-150, and miR-486 measured for MV, MV-free plasma, and brains from NI, NCM, and CM conditions, expressed as normalized values as compared to the expression of a panel of control miRNA in each case. [score:4]
The direction of regulation in CM conditions was the opposite for MV and brain tissue in the case of miR-150, miR-205, miR-193b, and miR-467a. [score:3]
The differential expression profiles of these selected miRNA (miR-146a, miR-150, miR-193b, miR-205, miR-215, miR-467a, and miR-486) were analyzed in mouse MV, MV-free plasma, and brain tissue by quantitative reverse transcription PCR (RT-qPCR). [score:3]
NI MV OpenArray RT-qPCR hsa-miR-328 − 2.5* ± 0.93Not tested [a] hsa-miR-335* − 3.0* ± 1.13Not tested [a] mmu-miR-16* 2.8** ± 0.65Not tested [a] mmu-miR-21* 5.0** ± 0.88Not tested [a] mmu-miR-297a* 5.8* ± 1.60Not tested [a] mmu-miR-685 3.0* ± 1.00Not tested [a] mmu-miR-1949 5.0* ± 1.69Not tested [a] hsa-miR-590-5p Unique to NINot validated [b] rno-miR-450 Unique to CMNot validated [b] mmu-miR-10b 2.7* ± 0.85Not validated [b] hsa-miR-146a 3.2** ± 0.68 7.2* ± 2.74 hsa-miR-150 1.8* ± 0.64 2.7 (ns) ± 2.26 hsa-miR-205 2.3* ± 0.75 − 0.5 (ns) ± 1.89 hsa-miR-486 2.3*** ± 0.18 4.7 (ns) ± 1. 45 mmu-miR-193b − 2.7** ± 0.62 − 7.5* ± 0 62 mmu-miR-215 2.1* ± 0.554.6 (ns) ± 99.39 [c] mmu-miR-467a − 2.0* ± 0.69 − 5.6 (ns) ± 0.96 The list of significantly differentially expressed miRNA in CM vs NI MV from the was compared with the results obtained by. [score:2]
The results are presented as follows: significant changes in MV – miR-146a and miR-193b, significant changes in the brain—miR-205, miR-215, and miR-467a, no significant changes—miR-150 and miR-486. [score:1]
The results of these are denoted as * = 0.05–0.01, ** = 0.01–0.0001, *** ≤ 0.0001 No significant change in the abundance of miR-150, miR-205, miR-215, miR-467a, and miR-486 in MV following Plasmodium infectionOf the seven miRNA of interest tested by RT-qPCR, miR-146a and miR-193b showed the same significant change in abundance as in the OpenArray (from Fig.   2b). [score:1]
The database was searched with the full names of each murine miRNA as per the ThermoFisher Scientific product information and miRBase version 21: mmu-miR-16-1-3p, mmu-miR-21a-3p, mmu-miR-146a-5p, mmu-miR-150-5p, mmu-miR-193b-3p, mmu-miR-205-5p, mmu-miR-215-5p, mmu-miR-297a-3p, mmu-miR-328-3p, mmu-miR-335-3p, mmu-miR-467a-5p, mmu-miR-486a-5p, mmu-miR-685, mmu-miR-1949, and rno-miR-10b-5p. [score:1]
All the remaining miRNA (Table  1, miR-146a, miR-150, miR-193b, miR-205, miR-215, mir-467a, and miR-486) were tested on MV samples as per the and also on MV-free plasma and brain tissue from NI, NCM, and CM mice. [score:1]
No significant change in the abundance of miR-150, miR-205, miR-215, miR-467a, and miR-486 in MV following Plasmodium infection. [score:1]
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28
[+] score: 16
We performed microarray analysis of miRNA expression of glioma cells silenced for TALNEC2 and found that silencing of TALNEC2 increased the expression of several tumor suppressor miRNAs such as miR-137, miR-124, miR-205, miR-7 and miR-492, whereas it decreased the expression of some oncomiRs such as miR-21, miR-155, miR-33b and miR-191. [score:9]
We found that silencing of TALNEC2 in U87 cells resulted in an increased expression of miRNAs associated with tumor suppression [38, 39] (e. g., let-7b, miR-7, miR-124, miR-137, miR-129-3p, miR-142-3p, miR-205, miR-376c, miR-492, miR-562 and miR-3144) and in a decrease in the expression of miRNAs associated with tumor promotion [38– 40] (e. g., miR-9, miR-21 miR-33b, miR-155, miR-191, miR-525-3p, and miR-767-3p). [score:7]
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29
[+] score: 12
Furthermore, microRNAs that promote epithelial differentiation by targeting the EMT TFs ZEB1/2 (members of the miR-200 family [29, 30] and miR-205 [31]) were all downregulated in OTBCs (Figure 5d). [score:6]
Levels of miRNA expression in OTBCs of miR-141, miR-200a, miR-200b, miR-200c, and miR-205 were normalized to those of the parental lines (p86 and p48). [score:3]
Compared with their parental lines, OTBCs upregulated the EMT TFs SNAIL, TWIST, and ZEB1/2 as well as microRNAs associated with EMT, such as miR-200s family members and miR-205. [score:3]
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30
[+] score: 11
Other miRNAs from this paper: mmu-mir-10b, mmu-mir-122, mmu-mir-92a-2, mmu-mir-221, mmu-mir-92a-1
In order to additionally evaluate transfection efficiency and assess, if the studied inhibitor had a functional impact within studied cell lines we co -transfected 1×10 [6] EC cells with 50nM miR-205-LNA -inhibitor or scramble control and 30 ng/μl of pLightSwitch_3′UTR reporter vector containing optimized target sequence complementary to the miR-205-5p (based on miRBase 16) cloned downstream of RenSP luciferase gene (Acitve Motif, Carlsbad, CA, US). [score:5]
Cg-Foxn1 < nu>/cmdb mice bearing endometrial cancer xenografts, which were intraperitoneally injected with nine dosages of 25 mg/kg of miR-205-LNA -inhibitor. [score:3]
Mice were randomly divided into three groups (five animals in each group) and were treated with miR-205-LNA -inhibitor, scramble control or PBS, respectively. [score:3]
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31
[+] score: 10
For example, miR-23 and miR-203 have been shown to enhance radiosensitivity by targeting IL8/Stat3 and IL8/AKT signalling pathway, respectively in nasopharyngeal carcinoma [24, 25]; miR-205 has been reported to function as a tumour radiosensitizer by inhibiting DNA repair pathway via down-regulation of ZEB1 and Ubc13 in breast cancer cells [26]; miR-15a/16 can enhance radiation sensitivity of NSCLC cells by targeting the TLR1/NF-κB signalling pathway [27]. [score:10]
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32
[+] score: 9
For example, miR-205 overexpression (GPA ID: GPAHSA100034) caused the down-regulation of transcription factor E2F1 in the LNCaP cell line, and its DEGs were significantly enriched for targets of E2F1 (p < 0.001), indicating that E2F1 may function as a key intermediate element of miR-205 -mediated regulatory cascades, which is consistent with previous studies 24. [score:9]
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33
[+] score: 9
miR-681 + ND miR-205 +miR-205 expression was down-regulated in breast cancer, but up-regulated in other types of cancer including lung cancer, bladder cancer and ovarian cancer [63]. [score:9]
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34
[+] score: 9
Other miRNAs from this paper: hsa-mir-205, hsa-mir-221, mmu-mir-221
Finally, drug resistance associated with this genetic signature is mediated by removing the inhibitory effect of miR-205 on the expression of Bcl-2 and the ATP -binding cassette transporters A2 and A5 related to MDR and malignant progression [16]. [score:5]
Recent evidence, however, showed that high levels of E2F1 and DNp73 downregulate miR-205, which, in turn, controls E2F1 accumulation. [score:4]
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35
[+] score: 9
Other miRNAs from this paper: mmu-mir-10a, mmu-mir-221, mmu-mir-222
To further explore how PTEN was up-regulated in lung cancer cells by SFE, we detected multiple known PTEN -targeting miRNAs including miR-10a, miR-205, miR-221, and miR-222. [score:6]
In the rescue assays, we observed that the anti-cancer effects of SFE were significantly inhibited by miR-10a, miR-205, miR-221, or miR-222 (Figure 3F). [score:2]
Moreover, to validate the biological function of these miRNAs in lung cancer cells, we transfected A549 and H1299 cells with mimics of miR-10a, miR-205, miR-221, or miR-222 with or without treatment of SFE. [score:1]
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36
[+] score: 9
These are miR-23b-5p and miR-205 which function as tumor suppressors in many ways [26, 51], miR-375-3p is well characterized as a valuable marker of disease progression for diagnosis and prognosis [reviewed in 54], and miR-384-5p. [score:3]
To discover the molecular mechanisms through which Runx1, Runx2, and the Runx -targeting miRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, drive prostate tumorigenesis, we interrogated well-accepted bioinformatics tools; DAVID [57, 58] and Ingenuity Pathway Analysis (IPA-www. [score:3]
Consistent with these observations is the fact that miRNAs predicted to target AR, such as miR-23b-5p, miR-181-5p, and miR-205-5p are constitutively reduced in TRAMP prostates. [score:3]
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37
[+] score: 9
In MDA-MB-231 cells expressing the OVOLs, we used to assess expression of miR-200 family members (miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR205, miR-203), relative to controls miR-U6 and miR16. [score:5]
We observed significant upregulation of miR-203 and miR-205 in epithelial cells (Figure 6F). [score:4]
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38
[+] score: 8
For example, hsa-miR-133a, hsa-miR-200b, hsa-miR-206, and hsa-miR-218 were considered as tooth tissue-specific miRNAs [4]; eight differentially expressed miRNAs were expressed during morphogenesis and seven were expressed in the incisor cervical loop containing the stem cell niche [1]; the three most highly expressed microRNAs in dental epithelium were identified as mmu-miR-24, mmu-miR-200c, and mmu-miR-205, while mmu-miR-199a-3p and mmu-miR-705 were found in dental mesenchyme [2]; and miR-200 was suggested to play an important role in the formation of incisor cervical loop during stem cell–fueled incisor growth [5]. [score:8]
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39
[+] score: 8
Here, we intended to identify suitable MREs for bladder cancer specific adenovirus -mediated TRAIL expression from the miRNAs with downregulated expression in bladder cancer, including miR-1 [18- 21], miR-99a [22], miR-100 [23], miR-101 [24, 25], miR-125b [23, 26, 27], miR-133a [18, 20, 21, 23, 28- 30], miR-143 [22, 23, 31- 33], miR-145 [21, 23, 29- 31, 34], miR-195-5p [35], miR-199a-3p [36], miR-200 [37, 38], miR-203 [39, 40], miR-205 [37], miR-218 [21, 41], miR-490-5p [42], miR-493 [43], miR-517a [44], miR-574-3p [45], miR-1826 [46] and let-7c [42]. [score:8]
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40
[+] score: 8
Although miRNA-205 has been shown to inhibit mRNA and protein expression of Lyn, c-Src, and c-Yes in A498 cells resulting in G0/G1 cell cycle arrest and apoptosis [41], and Lyn specifically reduced expression of miRNA-181b that represses the anti-apoptotic protein Mcl1 [42], we did not detect a change in miRNA expression (≥ or ≤1.5-fold) in the U87-CA-Lyn or U87-DN-Lyn cells as compared to U87-LV cells using the Human Cancer miRNA PCR Array (MAH-102A, Qiagen) (WM Liu and CL Gladson, unpublished data). [score:8]
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41
[+] score: 8
Downregulated miRs that are identified as putative hubs but that are not DE by the filtering criteria (miR-mmu-let-7a-5p, mmu-miR-23a-5p, mmu-miR-23a-3p, mmu-miR-205-5p) are also depicted as gray oblongs. [score:4]
Fourteen individual miRs belonging to six miR families (miR-125a-5p/125b-5p/351/670/4319, let-7, miR-126-3p, miR-205/205ab, miR-335/335-5p and miR-23abc/23b-3p) were downregulated during pneumonia (Supplementary Table  11). [score:4]
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42
[+] score: 8
Concomitant with the large induction of epithelial -associated genes and repression of mesenchymal regulators, MET -associated miRNAs miR-205-5p and the miR-200 family (miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-141-3p and miR-429-3p) [23- 26] were markedly upregulated (at least four-fold) in the Thy1- to SSEA1+ transition (Figure 2; Additional file 3). [score:5]
miRNAs associated with the MET (miR-200a, b, c-3p, miR-141-3p, miR-429-3p, miR-205-5p) [23- 26] were not differentially expressed between the piPSC lines and the stem cell lines, with the exception of miR-200c-3p. [score:3]
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43
[+] score: 8
Apart from global modulation of miRNA biogenesis, mutant p53 also affects expression of miRNAs, principally by downregulating tumor-suppressive miRNAs – miR-130b in endometrial cancer (24), miR-27a in breast cancer cells (MDA-MB-468) (25), miR-223 in breast and colon cells (26), let-7i in breast cancer and DLD1 cells (colorectal cancer) (27), and miR-205 (28), and elevating oncogenic miRNAs: miR-128-2 (29) and miR-155 in breast cancer cells (30) to mediate its oncogenic functions. [score:8]
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44
[+] score: 8
Compared to RFA alone, the combination of RFA and vaccine further augmented and amplified the expression of shared and novel tumor-suppressor microRNA transcripts, including miR-141, a microRNA recently shown to inhibit migration and invasion in colorectal carcinoma cells [48], and miR-205, a tumor suppressor implicated in preventing epithelial-to-mesenchymal transition and whose repression has been associated with poor prognosis [45], [63]. [score:8]
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45
[+] score: 8
A recent study reported that miR-181a and b, miR-199b, miR-135a and miR-205 targeted endogenous SIRT1 and downregulated its expression in mouse embryonic stem cells [28]. [score:8]
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46
[+] score: 7
Of these miRNAs, the relatively prominent upregulated miRNAs were hsa-miR-3656, hsa-miR-139-5p, hsa-miR-4796-5p, hsa-miR-330-5p, hsa-miR-4698, hsa-miR-3124-5p, hsv2-miR-H10, hsa-miR-133b, hsa-miR-515-3p, hsa-miR-516a-5p, hsa-miR-4762-5p, hsa-miR-4508, hsa-miR-27a-5p, hsa-miR-3120-5p, hsa-miR-133a, and hsa-miR-205-5p (>15-fold), and the relatively prominent downregulated miRNAs were hsa-miR-411-3p, hsa-miR-19b-3p, hsa-miR-152, and hsa-miR-142-5p (>15-fold). [score:7]
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47
[+] score: 7
Although our results confirmed a lower expression of miR-203 and miR-205 in DU145 and PC3 cells, only miR-205 was significantly decreased in LNCaP cells and human PCa samples, in agreement with previous observations [22, 47, 48]. [score:3]
MiR-31, miR-34b-3p, miR-205, miR-224 and miR-452 showed differential expression levels between normal, PIN and PCa matched samples (p<0.01 by Friedman test; Fig 3). [score:3]
MiR-205 expression level was lower in BPH compared to PIN (p = 0.0027; Fig 4B). [score:1]
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48
[+] score: 7
Hence, downregulation of miR200c and miR205 in the cycling hypoxia-selected subpopulation corroborates with the stem-like phenotype exhibited in this subpopulation. [score:4]
In addition to miRNA200c and miR205, the cycling hypoxia-selected subpopulation showed decreased miR215 expression (Figure 6e). [score:3]
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49
[+] score: 7
The quantitative RT-PCR analysis confirmed that all four of the selected up-regulated hsa (Homo sapiens)-miRNAs (miR-205, miR-182, miR-135b, and miR-455-3p) were significantly up-regulated in NPC tissues (Fig. 1C). [score:7]
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50
[+] score: 7
Most notable, among the up-regulated miRNAs were miR-205, miR-342 and miR-21, while miR-29c, miR-192, miR-30b and miR-200a were significantly down-regulated. [score:7]
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51
[+] score: 7
Other miRNAs from this paper: hsa-mir-10a, hsa-mir-205, hsa-mir-200c, mmu-mir-10a, mmu-mir-200c
This data should prove useful to understand the role of miRNAs in normal external ear development in mammals and might hint over miRNA involvement in the etiology of microtia [4] Data was validated by Whole mount in situ hybridization in a subset of miRNAs whose mRNA targets have been associated with external ear development and present clear differential spatiotemporal expression patterns (mmu-miR-10a, mmu-miR-200c and mmu-miR-205) [1], [2], [3], [5]. [score:7]
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52
[+] score: 6
Expression was quantified using ΔCt for miR-221 or standard curve for miR-133a, miR-192, and miR-205. [score:3]
Conversely, miR-205-5p showed a sex-chromosome bias (XX > XY) in gonadally intact mice and a sex bias (M > F) in gonadectomized mice fed a chow diet (Additional file 5: Figure S1C). [score:1]
Values for miR-192 and miR-205 were log [10]-transformed before statistical analysis. [score:1]
However, when mice were fed a high fat diet, miR-192-5p and miR-205-5p showed no sex or sex chromosome differences. [score:1]
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53
[+] score: 6
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-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-27a, hsa-mir-30a, hsa-mir-31, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-127, mmu-mir-9-2, mmu-mir-141, mmu-mir-145a, mmu-mir-155, mmu-mir-10b, mmu-mir-24-1, mmu-mir-206, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10b, hsa-mir-34a, hsa-mir-205, hsa-mir-221, mmu-mir-290a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-141, 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-206, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, 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-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-24-2, mmu-mir-27a, mmu-mir-31, mmu-mir-34a, mmu-mir-103-1, mmu-mir-103-2, mmu-mir-322, hsa-mir-200c, hsa-mir-155, mmu-mir-17, mmu-mir-25, mmu-mir-200c, mmu-mir-221, mmu-mir-29b-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, hsa-mir-106b, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-373, hsa-mir-20b, hsa-mir-520c, hsa-mir-503, mmu-mir-20b, mmu-mir-503, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-126b, mmu-mir-290b, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
The overexpression of certain oncogenic miRNAs (miR-21, miR-27a, miR-155, miR-9, miR-10b, miR-373/miR-520c, miR-206, miR-18a/b, miR-221/222) and the loss of several tumor suppressor miRNAs (miR-205/200, miR-125a, miR-125b, miR-126, miR-17-5p, miR-145, miR-200c, let-7, miR-20b, miR-34a, miR-31, miR-30) lead to loss of regulation of vital cellular functions that are involved in breast cancer pathogenesis [127, 128]. [score:6]
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54
[+] score: 6
Compared to ALK(−) ALCLs, miR-203, miR-135b, miR-886-5p/3p, miR-20b, miR-106a and miR-183 were significantly upregulated in ALK(+) ALCLs while others (miR-155, miR-181a, miR-210, miR-29a/b, miR-342-5p/3p, miR-369-3p miR-374a/b, miR-423-5p, miR-625, miR-205, miR-146a and miR-26a) were down-regulated (Table 1). [score:6]
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55
[+] score: 6
MiR-205 and miR-181d were uniquely expressed and stress responsive in the thymic tissue. [score:3]
MiR-125b-5p, miR-150, miR-205, and miR-342-3p were consistently up regulated in the thymic tissue from the LPS injected mice (Figure 2B). [score:2]
The individual miRs (miR-150, miR-205, miR-128, miR-181a, miR-181b, miR-181d) were detected by Northern blotting. [score:1]
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[+] score: 6
Other miRNAs from this paper: mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-140, mmu-mir-141, mmu-mir-152, mmu-mir-182, mmu-mir-183, mmu-mir-191, mmu-mir-199a-1, mmu-mir-200b, mmu-let-7d, 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-96, mmu-mir-200c, mmu-mir-214, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-182, dre-mir-183, dre-mir-199-1, dre-mir-199-2, dre-mir-199-3, dre-mir-205, dre-mir-214, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, mmu-mir-429, mmu-mir-449a, dre-mir-429a, 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-96, 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-140, dre-mir-141, dre-mir-152, 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, dre-let-7j, mmu-mir-449c, mmu-mir-449b, dre-mir-429b, mmu-let-7j, mmu-let-7k, mmu-mir-124b
By contrast, we identified 12 miRNAs corresponding to 9 families (miR-199, miR-140, miR-152, miR-214, miR-205, miR-200, miR-183, miR-182, miR-96) that displayed highly enriched expression in the olfactory system (Figure 1A). [score:3]
Five of 24 probes, including miR-449 and miR-205, displayed expression limited to the nonneural respiratory epithelium (Figure 2A, left column, and Table S3). [score:3]
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57
[+] score: 6
A number of studies have shown that miRNAs, such as miR-34, miR-125, miR-200, miR-205, miR-328, and miR-30, were down-regulated and acted as tumor suppressors in breast cancer [16– 22]. [score:6]
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At the opposite, miR-133 and miR-205 display a significant increased expression level in Dicer1 c KO compared to control group. [score:2]
Ctrl)↑ in Dicer1 c KO mmu-miR-138-5p -26,449 0,00106 mmu-miR-204-3p -4,49045 0,00140 mmu-miR-425-5p -4,24086 0,00380 mmu-miR-672-5p -3,74912 0,00271 mmu-miR-99b-3p -2,71028 0,00362 mmu-miR-191-5p -2,65916 0,00001 mmu-miR-200c-3p -2,57172 0,00340 mmu-miR-671-3p -2,47448 0,00744 mmu-miR-652-3p -2,14466 0,00837↓ in Dicer1 c KO mmu-miR-205-5p 2,07404 0,00226 mmu-miR-7019-5p 2,12703 0,00265 mmu-miR-7653-5p 2,3651 0,00209 mmu-miR-466m-5p 3,2093 0,00585 mmu-miR-669m-5p 3,2093 0,00585 We used qRT-PCR to assess the detection level of eight mature miRNA candidates whose expression intensity is changed in the proximal epididymidis of Dicer1 c KO compared with control mice (Fig 1B). [score:2]
Ctrl)↑ in Dicer1 c KO mmu-miR-138-5p -26,449 0,00106 mmu-miR-204-3p -4,49045 0,00140 mmu-miR-425-5p -4,24086 0,00380 mmu-miR-672-5p -3,74912 0,00271 mmu-miR-99b-3p -2,71028 0,00362 mmu-miR-191-5p -2,65916 0,00001 mmu-miR-200c-3p -2,57172 0,00340 mmu-miR-671-3p -2,47448 0,00744 mmu-miR-652-3p -2,14466 0,00837↓ in Dicer1 c KO mmu-miR-205-5p 2,07404 0,00226 mmu-miR-7019-5p 2,12703 0,00265 mmu-miR-7653-5p 2,3651 0,00209 mmu-miR-466m-5p 3,2093 0,00585 mmu-miR-669m-5p 3,2093 0,00585We used qRT-PCR to assess the detection level of eight mature miRNA candidates whose expression intensity is changed in the proximal epididymidis of Dicer1 c KO compared with control mice (Fig 1B). [score:2]
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59
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It was also shown that miR-184 can interfere with the ability of miR-205 to suppress SHIP2 level, indicating that one miRNA could abrogate the inhibitory function of another [27]. [score:5]
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60
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Indeed, inhibition of miR-712 (or its human homologue miR-205) prevented endothelial inflammation and atherosclerosis in a carotid ligation mo del [34] and aortic dilatation, elastin fragmentation, and aortic rupture in Apoe [−/−] mice, [62] potentially through post-transcriptional regulation of TIMP-3 and associated heightened MMP activity. [score:4]
Kim CW Kumar S Son DJ Jang IH Griendling KK Jo H Prevention of abdominal aortic aneurysm by anti-microRNA-712 or anti-microRNA-205 in angiotensin II-infused mice. [score:1]
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61
[+] score: 5
Other miRNAs from this paper: mmu-mir-141, mmu-mir-200b, mmu-mir-200a, mmu-mir-200c, mmu-mir-429
Previous studies have shown that expression of microRNA-200 family members and microRNA-205 in particular is necessary for the maintenance of the epithelial phenotype [18, 19], that is, the reverse of EMT activity; thus, we further validated the RNA transcript and microRNA array expression results. [score:5]
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62
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Other miRNAs from this paper: hsa-mir-205
Su C. Lee W. Wu A. T. H. Lin Y. Wang L. Wu C. Yeh C. Pterostilbene inhibits triple -negative breast cancer metastasis via inducing microRNA-205 expression and negatively modulates epithelial-to-mesenchymal transition J. Nutr. [score:5]
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63
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Furthermore, let-7, miR-15a, miR-31, miR-34, miR-205 and others were demonstrated to suppress Ras, Myc, Bcl2, Notch, E2F1 or CyclinD1 [14], suggesting a tumor-suppressive activity for these miRNAs. [score:5]
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64
[+] score: 5
miR-203 and miR-205 expression in esophageal squamous cell carcinoma is significantly lower than in normal epithelial tissues, while the expression of miR-21 is significantly higher than in the normal epithelial tissues [1]. [score:5]
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65
[+] score: 5
MiRNAs have been found to regulate cell proliferation, differentiation, and apoptosis [15- 17] and they have also been implicated in the regulation of senescence (miR-29, miR-30, miR-34a, miR-34b, miR-34c, miR122 miR-203, miR-205 and miR-217) [18- 23] mostly by interfering with either the p53 pathway or the retinoblastoma RB1/E2F function. [score:3]
Two independent research groups have reported a miRNA -dependent induction of senescence in MM cell lines with a focus on miR-205/miR-203-E2F axis [23, 25]. [score:1]
MiR -dependent induction of cellular senescence in MM has recently and independently been demonstrated by other researchers for miR-203 and miR-205 in cutaneous MM and for miR-34a in uveal MM [23, 25, 50]. [score:1]
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66
[+] score: 5
Similarly, other investigators have also shown that FOXQ1 played a key role in nasopharyngeal carcinoma, targeted by miR-506 and miR-124 [29, 30]; likewise, HMGB3 in breast cancer is targeted by miR-205 [31]; and MKI67 in hepatocellular carcinoma, targeted by miR-519d [32]. [score:5]
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67
[+] score: 5
MicroRNA-205 regulates the expression of Parkinson’s disease-related leucine-rich repeat kinase 2 protein. [score:5]
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68
[+] score: 4
Down-regulation of miR-205 by HER2 is shown to enhance tumorigenesis in breast cancer. [score:4]
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69
[+] score: 4
In addition, after subcutaneous injection of S. aureus, no up-regulated miRNAs were detected in the whole blood at 4 h and 8 h. At 24 h after S. aureus injection, the levels of 7 miRNAs (miR-133b, miR-133a, miR-122, miR-205, miR-1899, miR-714, and miR-291b) increased significantly (Table 3). [score:4]
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70
[+] score: 4
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-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-32, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-137, mmu-mir-140, mmu-mir-150, mmu-mir-155, mmu-mir-24-1, mmu-mir-193a, mmu-mir-194-1, mmu-mir-204, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-143, mmu-mir-30e, hsa-mir-34a, hsa-mir-204, hsa-mir-205, hsa-mir-222, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-137, hsa-mir-140, hsa-mir-143, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-150, hsa-mir-193a, hsa-mir-194-1, 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-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-23a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-92a-2, mmu-mir-34a, rno-mir-322-1, mmu-mir-322, rno-let-7d, rno-mir-329, mmu-mir-329, rno-mir-140, rno-mir-350-1, mmu-mir-350, hsa-mir-200c, hsa-mir-155, mmu-mir-17, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-33, mmu-mir-222, mmu-mir-135a-2, mmu-mir-19b-1, mmu-mir-92a-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-375, mmu-mir-375, mmu-mir-133b, hsa-mir-133b, 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-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-17-1, rno-mir-19b-1, rno-mir-19b-2, rno-mir-23a, rno-mir-24-1, rno-mir-24-2, rno-mir-25, rno-mir-27b, rno-mir-29a, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-31a, rno-mir-32, rno-mir-33, rno-mir-34a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-106b, rno-mir-126a, rno-mir-135a, rno-mir-137, rno-mir-143, rno-mir-150, rno-mir-193a, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-204, rno-mir-205, rno-mir-222, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, mmu-mir-410, hsa-mir-329-1, hsa-mir-329-2, mmu-mir-470, hsa-mir-410, hsa-mir-486-1, hsa-mir-499a, rno-mir-133b, mmu-mir-486a, hsa-mir-33b, rno-mir-499, mmu-mir-499, mmu-mir-467d, hsa-mir-891a, hsa-mir-892a, hsa-mir-890, hsa-mir-891b, hsa-mir-888, hsa-mir-892b, rno-mir-17-2, rno-mir-375, rno-mir-410, mmu-mir-486b, rno-mir-31b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-126b, rno-mir-9b-2, hsa-mir-499b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, hsa-mir-486-2, mmu-mir-126b, rno-mir-155, rno-let-7g, rno-mir-15a, rno-mir-196b-2, rno-mir-322-2, rno-mir-350-2, rno-mir-486, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
For instance, among the 66 uniformly expressed miRNAs for which IPA assigned functions, we identified 12 candidates that have been implicated in androgen regulation, including: let-7a-5p, miR-15a-5p, miR-17-5p, miR-19b-3p, miR-23a-3p, miR-24-3p, miR-27b-3p, miR-30a-5p, miR-34a-5p, miR-140-5p, miR-193a-3p, miR-205-5p (S1 Fig). [score:4]
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71
[+] score: 4
Gregory PA The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1Nat. [score:4]
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72
[+] score: 4
In addition, miR-106a, miR-146, miR-155, miR-150, miR-17-3p, miR-191, miR-197, miR-192, miR-21, miR-203, miR-205, miR-210, miR-212, and miR-214 have been reported to be up-regulated in lung cancer [12]. [score:4]
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73
[+] score: 4
Skourti E. Logotheti S. Kontos C. K. Pavlopoulou A. Dimoragka P. T. Trougakos I. P. Gorgoulis V. Scorilas A. Michalopoulos I. Zoumpourlis V. Progression of mouse skin carcinogenesis is associated with the orchestrated deregulation of mir-200 family members, mir-205 and their common targetsMol. [score:4]
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74
[+] score: 4
Other miRNAs from this paper: mmu-mir-200b, mmu-mir-200a, mmu-mir-200c, mmu-mir-429
Gregory PA The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1Nat. [score:4]
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75
[+] score: 4
Gregory PA The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1Nat Cell Biol. [score:4]
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76
[+] score: 4
E14.5) microRNA 205; RIKEN cDNA 4631405K08 gene Mir205 - - -2.38 microRNA 669d Mir669d - - -2.07 glutamate-ammonia ligase (glutamine synthetase); microRNA 8114 Glul - - 2.14 microRNA 130a Mir130a - - 2.28miRNAs reported as downregulated in ageing skeletal muscle are written in bold text [39]. [score:4]
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77
[+] score: 4
In our study miR-205-5p expression was six times higher in old than young N mice, although it did not change in df/df mice with age. [score:3]
Serum miR-205 was higher in ovarian cancer patients and had the best diagnostic accuracy [68]. [score:1]
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78
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Among the miRNAs upregulated in rat PSCs, we also identified miR-205 and members of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429), which promote mesenchymal to epithelial transition (MET) in mouse cells, a key step in fibroblast reprogramming [47]. [score:4]
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79
[+] score: 3
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-96, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-141, mmu-mir-152, mmu-mir-182, mmu-mir-183, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-205, hsa-mir-214, hsa-mir-200b, mmu-let-7d, mmu-mir-130b, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-141, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, 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-96, hsa-mir-200c, mmu-mir-200c, mmu-mir-214, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-200a, hsa-mir-130b, hsa-mir-376a-1, mmu-mir-376a, dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-182, dre-mir-183, dre-mir-199-1, dre-mir-199-2, dre-mir-199-3, dre-mir-205, dre-mir-214, hsa-mir-429, mmu-mir-429, hsa-mir-450a-1, mmu-mir-450a-1, dre-mir-429a, 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-96, 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-130b, dre-mir-141, dre-mir-152, dre-mir-200a, dre-mir-200b, dre-mir-200c, hsa-mir-450a-2, dre-let-7j, hsa-mir-376a-2, mmu-mir-450a-2, dre-mir-429b, mmu-let-7j, mmu-let-7k, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
The most abundant miRs expressed in the developing mouse OE are: the miR-200-class (- 200a, - 200b, - 200c, - 141 and - 429), miR-199, miR-152, miR-214, miR-205, miR-183, miR-182 and miR-96 (Choi et al., 2008). [score:3]
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80
[+] score: 3
A further two (miR-205-5p, miR-340-5p) agreed with the direction of regulation due to a father’s HFD, but did not reach statistical significance due to the large variance detected across the limited sample size used in the Taqman array (ie n = 4), mainly between the HFD father samples. [score:3]
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81
[+] score: 3
miR-1, along with miR-133a, miR-205 and let-7d, showed decreased expression in SCCs of the head and neck in comparison to normal adjacent tissue (Childs et al., 2009). [score:3]
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82
[+] score: 3
Only a few miRNA from the selected group had validated target genes: miR-155, miR-21, miR-125a, miR-31, miR-205, miR-20a, let-7f, miR-182, let-7e, miR-199b, miR-199a, miR-663, and miR-193a. [score:3]
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83
[+] score: 3
miR-205 is a critical regulator of lacrimal gland development. [score:3]
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84
[+] score: 3
As a control, the total list of miRNAs profiled was randomized in order and 9 miRNAs were selected (miR-452, miR-7, miR-205, miR-15a, miR-144, miR-183, miR-463, miR-25, miR-99a), targets and pathway ontology was analyzed as for the candidate list. [score:3]
[1 to 20 of 1 sentences]
85
[+] score: 3
Moreover, cofilin is indirectly regulated by miR-205 via Rho-ROCKI activity in keratinocytes (Yu et al., 2010). [score:3]
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86
[+] score: 3
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-21, hsa-mir-23a, hsa-mir-30a, hsa-mir-98, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-30a, mmu-mir-30b, mmu-mir-101a, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-132, mmu-mir-133a-1, mmu-mir-135a-1, mmu-mir-150, mmu-mir-155, mmu-mir-204, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-34a, hsa-mir-204, hsa-mir-205, hsa-mir-217, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-150, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, 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-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-23a, mmu-mir-34a, mmu-mir-98, mmu-mir-322, mmu-mir-338, hsa-mir-155, mmu-mir-17, mmu-mir-19a, mmu-mir-135a-2, mmu-mir-19b-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, mmu-mir-217, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-30e, hsa-mir-338, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, hsa-mir-18b, hsa-mir-503, mmu-mir-541, mmu-mir-503, mmu-mir-744, mmu-mir-18b, hsa-mir-541, hsa-mir-744, mmu-mir-133c, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
A previous study showed that runx2 is a target of miR-30c, miR-135a, miR-204, miR-133a, miR-217, miR-205, miR-34, miR-23a and miR-338 [34]. [score:3]
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87
[+] score: 3
In addition, the expression levels of several oncomiRs such as miR-205 and miR-221 were significantly induced by 5-fluorouracil and pirarubicin treatment (Figure. [score:3]
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88
[+] score: 3
Noguchi S. Iwasaki J. Kumazaki M. Mori T. Maruo K. Sakai H. Yamada N. Shimada K. Naoe T. Kitade Y. Chemically modified synthetic microRNA-205 inhibits the growth of melanoma cells in vitro and in vivo Mol. [score:3]
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89
[+] score: 3
In accordance, we found that expression of miR200a, miR200b, miR200c, miR429 and miR205 was significantly reduced in Pten [Δf]:p53 [Δf] versus Pten [Δf] tumors (Supplementary Fig S3B and C, Supplementary Table S1F). [score:3]
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90
[+] score: 3
Previous studies have identified miR-21, miR-27, miR-96, miR-128, miR-155 and miR-182 as oncogenes, and miR-17, miR-27, miR-125, miR-145, miR-205 and miR-206 as tumor suppressor genes [13- 15]. [score:3]
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91
[+] score: 2
In recent studies, miRNAs including miR-148a [8], miR-200c [9], miR-205 [2, 9], miR-21 [10], miR-31 [2], and miR-34 [11], have been reported to regulate drug resistance in PC. [score:2]
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92
[+] score: 2
Other miRNAs from this paper: hsa-mir-205, mmu-mir-712
AngII infusion could induce endothelial miR-712/miR-205 in AAA, both in vitro and in vivo, and the silencing of miR-712/miR-205 by antisense oligonucleotides could decrease inflammation and the activity of endothelail MMPs, thus preventing AAA development in AngII-infused ApoE [−/−] mice 52. [score:2]
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93
[+] score: 2
MicroRNAs, such as hsa-miR-503, hsa-miR-205, and hsa-miR-200b, have been shown to be dysregulated in endometrioid endometrial carcinoma (EEC) [1, 2]. [score:2]
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94
[+] score: 2
Identification of MiR-205 As a MicroRNA That Is Highly Expressed in Medullary Thymic Epithelial Cells. [score:2]
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95
[+] score: 2
The only microRNA able to distinguish cancer subtypes was miR-205. [score:1]
Quantitative real-time PCR was used to determine levels of miR-99a (Hs04231437_s1), miR-205 (ID 000509), Nanog (Hs04399610_g1), Oct3/4 (Hs04260367_gH), Sox2 (Hs01053049_s1), Snail (Hs00161904_m1), Twist (Hs01675818_s1) and housekeeping genes U6 (ID 0001093), TBP (Hs00427620_m1) and IPO8 (Hs00183533_m1) using the Assays-on-Demand Taqman Gene Expression Assays (Applied Biosystems, Foster City, CA, USA) according to the procedure previously described. [score:1]
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96
[+] score: 2
Several miRs, such as miR-133b, miR-7 and miR-153, miR-433, let-7a-5p and miR-184-5p, miR-205, miR-132 and miR-34b/c, have previously been implicated in the development and maintenance of DA neurons and were linked to neurodegeneration. [score:2]
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97
[+] score: 2
Other miRNAs from this paper: mmu-mir-200b, mmu-mir-200a, mmu-mir-200c
Twist cooperation with Slug is necessary for EMT induction in mammary epithelial cells [5], while deregulation of miR-200c and miR-205 leads to EMT that is associated with clinically relevant insensitivity to docetaxel in prostate cells [6]. [score:2]
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98
[+] score: 2
Out of these 29 miRNAs detected at comparable levels, six miRNAs (miR-205, miR-200c, miR-200b, miR-148a, miR-203, miR-24) were found to be expressed at markedly lower levels in MDA-MB-231 cells compared to HMEC cells (top 6 miRNAs in Figure 1A). [score:2]
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99
[+] score: 1
Also, the miR-200 family and miR-205 were shown to be repressed by TWIST1 [52]. [score:1]
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100
[+] score: 1
[6] miR-205 has been shown to exert negative effects on the osteogenic differentiation of BMSCs, [7] whereas miR-21 promoted the osteogenic differentiation of MSCs via the PI3K/β-catenin pathway. [score:1]
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