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

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. © 2016 the author(s).