Mir-335 Suppresses Ovarian Caner Invasion By Targeting Bcl-w

Aberrant expression of miR-335 has been reported in various cancers. Although it has been associated with ovarian cancer, whether it is an active participant or a mere bystander remains unknown. To clarify its role in ovarian carcinogenesis, we first examined the relative expression of miR-335 in 95 ovarian tissues using qRT-PCR. We found that miR-335 was downregulated in primary ovarian cancers relative to normal ovaries and low miR-335 was correlated with poorer clinical outcomes in ovarian cancer. In our 5 paired cases, omental metastases had even lower levels of miR335 than corresponding primary tumors, suggesting that selective pressures diminish the prevalence of miR-335 expressing cells during the course of metastatic progression. Bioinformatics search revealed that an anti-apoptotic gene, Bcl-w, was among its potential targets. On restoration of miR-335, the invasive potentials of adenocarcinoma SKOV3 and ovarian clear cell carcinoma ES2 cell lines were suppressed and a concomitant inhibition of cellular Bcl-w was also observed. These suppressive effects did not involve confounding influences on tumor proliferation and was largely attributable to miR-335's ability to target Bcl-w, as indicated by the fact that ectopic Bcl-w could almost fully nullify ectopic miR-335-imposed invasion suppression. These findings indicate that decreased miR-335 elevates the expression of its target, Bcl-w, which in turn contributes to the promotion of ovarian cancer invasion.