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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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Title: MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells
Authors: Dong, Peixin Browse this author →KAKEN DB
Xiong, Ying Browse this author
Watari, Hidemichi Browse this author →KAKEN DB
Hanley, Sharon J. B. Browse this author →KAKEN DB
Konno, Yosuke Browse this author
Ihira, Kei Browse this author
Yamada, Takahiro Browse this author →KAKEN DB
Kudo, Masataka Browse this author
Yue, Junming Browse this author
Sakuragi, Noriaki Browse this author →KAKEN DB
Keywords: microRNA-137
Cancer stemness
Ovarian cancer
Issue Date: 5-Sep-2016
Publisher: BioMed Central
Journal Title: Journal of Experimental & Clinical Cancer Research
Volume: 35
Start Page: 132
Publisher DOI: 10.1186/s13046-016-0415-y
Abstract: 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.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 董 培新

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