miR-137 Modulates a Tumor Suppressor Network-Inducing Senescence in Pancreatic Cancer Cells

Neault, Mathieu; Mallette, Frédérick A.; Richard, Stéphane

doi:10.1016/j.celrep.2016.01.068

Cited by 70 publications

(60 citation statements)

References 78 publications

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“…It is well known that abnormal expression of miRNAs is closely related to regulation of cancer initiation and progression, and function as oncogene or tumor suppressor genes in many malignant tumors . Studies conducted on miR‐137 have provided evidences that miR‐137 is downregulated and functions as a tumor suppressor in a variety of human cancers, including various gastrointestinal cancers: colorectal cancer, hepatocellular cancer, gastric cancer, and pancreatic cancer …”

Section: Introductionmentioning

confidence: 99%

RETRACTED: MiR‐137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP

Ding

Zhang

Gao

et al. 2018

J of Cellular Biochemistry

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miRNAs are small noncoding RNAs that act as critical epigenetic regulators in tumor carcinogenesis. In this study, our data showed that miR-137 was significantly downregulated in 58 pairs of human pancreatic cancer (PanCa) tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated with increased tumor size, higher TNM stage, and worse prognosis in pancreatic cancer. Functional studies demonstrated that overexpression of miR-137 dramatically suppressed cell proliferation and induced cell apoptosis in vitro. Meanwhile, upregulated miR-137 remarkably inhibited migration and invasion of pancreatic cancer cells. Further studies indicated that MRGBP was identified as the direct downstream target gene of miR-137. In addition, MRGBP expression is significantly downregulated in miR-137-transfected cells. Our previous study revealed that silencing of MRGBP suppressed the growth of PanCa cells in vitro and in vivo and also promoted apoptosis, and inhibited migration and invasion of PanCa cells, which are consistent with the effects of miR-137 overexpression. Taken together, our findings suggest that miR-137 may function as a novel tumor promoter through directly targeting MRGBP in PanCa.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: MiR‐137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP

Ding

Zhang

Gao

et al. 2018

J of Cellular Biochemistry

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“…Thus, in addition to regulation of KDM4A by miR-137 and miR-23a in pancreatic cancer and breast cancer, 22,23 we identified miR-10a as a new regulator of KDM4A in PCa. KDM4A cooperated with ETV1 to increase expression of YAP and its target genes.…”

Section: Discussionmentioning

confidence: 84%

MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A

Xiang

et al. 2018

J of Cellular Biochemistry

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Deregulation of microRNAs contributes to the abnormal cell growth which is frequently observed in cancer. In the current study, we detected the expression and regulatory relationship between miR‐10a and Lysine‐specific demethylase 4A (KDM4A) to reveal their function in prostate cancer (PCa) progression. We found that miR‐10a levels were significantly decreased in PCa cell lines in comparison with the normal epithelial cell line RWPE‐1. Downregulation of miR‐10a levels was also observed in tumor tissues from PCa patients compared with the adjacent normal tissues. Enhanced expression of miR‐10a inhibited cell proliferation and colony forming capability of PCa cells. In addition, quantitative real‐time polymerase chain reaction and Western blot analysis showed a significant decrease of KDM4A in response to miR‐10a elevation in PCa cells. Using dual luciferase assay, we confirmed that KDM4A was a target gene for miR‐10a. Furthermore, Western blot analysis indicated that miR‐10a overexpression inactivated YAP signaling and suppressed transcription of YAP target genes. Additionally, cell growth arrest and colony forming capacity inhibition induced by miR‐10a overexpression could be reversed by YAP overexpression in PCa cells. More importantly, miR‐10a mimics inhibited PC‐3 tumor growth in nude mice accompanied with a remarkable reduction of KDM4A and YAP expression. In conclusion, our results uncovered a tumor suppressor role of miR‐10a in PCa via negative regulation of KDM4A and its downstream Hippo‐YAP pathway.

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“…Downregulation of the miR-130b–301b cluster impairs cellular senescence in prostate cancer [29], while miR-494-3p increases the radiosensitivity of oral squamous cell carcinoma cells through the induction of cellular senescence caused by the downregulation of Bmi1 [30]. Restoration of miR-137 expression inhibited proliferation and promoted senescence of pancreatic cancer cells [31]. Cellular senescence is a state of irreversible proliferative arrest that results in a senescent phenotype, which is characterized by increased SA-β-gal activity, inhibited cell proliferation and cell-cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer

Zheng

Wei

et al. 2017

J Exp Clin Cancer Res

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BackgroundMicroRNAs are endogenously expressed, small non-coding RNAs that modulate gene expression by targeting specific mRNAs, resulting in translational repression or mRNA degradation. Although miR-584-5p has been reported to play a vital role in various malignancies, its role and the molecular mechanisms underlying the effects of miR-584-5p in gastric cancer (GC) remain to be clarified. In this study, we investigated the role of miR-584-5p in GC.MethodsThe expression of miR-584-5p and its specific target gene were determined in human GC specimens and cell lines by microRNA real-time polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR) and Western blot. The effects of miR-584-5p depletion or ectopic expression on GC proliferation were evaluated in vitro using CCK-8 proliferation assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation assays and cell-cycle assays and the in vivo effects were investigated using a mouse tumorigenicity model. Cell apoptosis was evaluated by in vitro flow cytometric analysis, cell viability assays and in vivo TUNEL assays. Luciferase reporter assays were employed to identify interactions between miR-584-5p and its specific target gene.ResultsA series of in vitro and in vivo gain- and loss-of-function assays revealed that miR-584-5p inhibited GC cell proliferation, while apoptosis was induced. Luciferase reporter assays and Western blot analysis revealed WWP1 to be a direct target of miR-584-5p. The effects of miR-584-5p-mimic were rescued by WWP1 overexpression. In contrast, the effects of the miR-584-5p-inhibitor were impaired by WWP1-shRNA. Furthermore, miR-584-5p expression levels correlated negatively with WWP1 protein expression in GC tissues and GC cell lines. A series of investigations indicated that miR-584-5p promoted senescence and activated the TGFβ signaling pathway by downregulation of WWP1.ConclusionTaken together, these results suggest that downregulation of miR-584-5p contributes to tumor progression by downregulation of WWP1, thus, highlighting the potential of miR-584-5p as a therapeutic target for human GC.

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miR-137 Modulates a Tumor Suppressor Network-Inducing Senescence in Pancreatic Cancer Cells

Cited by 70 publications

References 78 publications

RETRACTED: MiR‐137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP

RETRACTED: MiR‐137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP

MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A

Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer

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