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MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells


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タイトル: MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells
著者: Dong, Peixin 著作を一覧する
Xiong, Ying 著作を一覧する
Watari, Hidemichi 著作を一覧する
Hanley, Sharon J. B. 著作を一覧する
Konno, Yosuke 著作を一覧する
Ihira, Kei 著作を一覧する
Yamada, Takahiro 著作を一覧する
Kudo, Masataka 著作を一覧する
Yue, Junming 著作を一覧する
Sakuragi, Noriaki 著作を一覧する
キーワード: microRNA-137
Cancer stemness
Ovarian cancer
発行日: 2016年 9月 5日
出版者: BioMed Central
誌名: Journal of Experimental & Clinical Cancer Research
巻: 35
開始ページ: 132
出版社 DOI: 10.1186/s13046-016-0415-y
抄録: Background: In ovarian cancer (OC) cells, Snail was reported to induce the epithelial-to-mesenchymal transition (EMT), which is a critical step in OC metastasis. At present little is known about controlling Snail expression in OC cells by using specific microRNAs (miRNAs). Methods: We first used a computational target prediction analysis to identify 6 candidate miRNAs that bind to the 3′-untranslated region (3′-UTR) region of the Snail mRNA. Among these miRNAs, two miRNAs (miR-137 and miR-34a) with a potential to regulate Snail were validated by quantitative real-time PCR, Western blot analysis, and Snail 3′-UTR reporter assays. We assessed the effects of miR-137 and miR-34a on EMT, invasion and sphere formation in OC cells. We also evaluated the expression of miR-137 and miR-34a in OC tissues and adjacent normal tissues and analyzed the relationship between their expression and patient survival. Results: We report that OC tissues possess significantly decreased levels of miR-137 and miR-34a and increased expression of Snail when compared to their adjacent normal tissues, and lower miR-137 and miR-34a expression correlates with worse patient survival. Using luciferase constructs containing the 3′-UTR region of Snail mRNA combined with miRNA overexpression and mutagenesis, we identified miR-137 and miR-34a as direct suppressors of Snail in OC cells. The introduction of miR-137 and miR-34a resulted in the suppression of Snail at both the transcript and protein levels, and effectively suppressed the EMT phenotype and sphere formation of OC cells. However, the inhibition of miR-137 and miR-34a with antisense oligonucleotides promoted EMT and OC cell invasion. Moreover, ectopic expression of Snail significantly reversed the inhibitory effects of miR-137 and miR-34a on OC cell invasion and sphere formation. Conclusions: These findings suggest that both miR-137 and miR-34a act as Snail suppressors to negatively regulate EMT, invasive and sphere-forming properties of OC cells.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 董 培新


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