MicroRNA-182 promotes cell growth, invasion, and chemoresistance by targeting programmed cell death 4 (PDCD4) in human ovarian carcinomas

As an important tumor suppressor, programmed cell death 4 (PDCD4) influences transcription and translation of multiple genes, and modulates different signal transduction pathways. However, the upstream regulation of this gene is largely unknown. In this study, we found that microRNA‐182 (miRNA‐182,...

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Published inJournal of cellular biochemistry Vol. 114; no. 7; pp. 1464 - 1473
Main Authors Wang, Yu-Quan, Guo, Ren-De, Guo, Rui-Meng, Sheng, Wei, Yin, Li-Rong
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2013
Wiley Subscription Services, Inc
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Summary:As an important tumor suppressor, programmed cell death 4 (PDCD4) influences transcription and translation of multiple genes, and modulates different signal transduction pathways. However, the upstream regulation of this gene is largely unknown. In this study, we found that microRNA‐182 (miRNA‐182, miR‐182) was upregulated, whereas PDCD4 was downregulated in ovarian cancer tissues and cell lines. Blocking or increase of miR‐182 in ovarian cancer cell lines led to an opposite alteration of endogenous PDCD4 protein level. Using fluorescent reporter assay, we confirmed the direct and negative regulation of PDCD4 by miR‐182, which was dependent on the predicted miR‐182 binding site within PDCD4 3′ untranslated region (3′ UTR). MTT and colony formation assays suggested that miR‐182 blockage suppressed, whereas miR‐182 mimics enhanced viability and colony formation of ovarian cancer cells. These effects may partly be attributed to the cell cycle promotion activity of miR‐182. miR‐182 also contributed to migration and invasion activities of ovarian cancer cells. Furthermore, miR‐182 reduced the chemosensitivity of ovarian cancer cells to CDDP and Taxol, possibly by its anti‐apoptosis activity. Importantly, all the alterations of the above cellular phenotypes by blocking or enhancing of miR‐182 could be alleviated by subsequent suppression or ectopic expression of its target PDCD4, respectively. We conclude that in ovarian cancer cells, miR‐182 acts as an oncogenic miRNA by directly and negatively regulating PDCD4. J. Cell. Biochem. 114: 1464–1473, 2013. © 2013 Wiley Periodicals, Inc.
Bibliography:istex:350BA5BA1A5A2C2B69B9C0CDC189EADE5D593745
ArticleID:JCB24488
We declare that we have no conflict of interest.
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SourceType-Scholarly Journals-1
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content type line 23
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.24488