miR-335 represents an invasion suppressor gene in ovarian cancer by targeting Bcl-w

Abstract

microRNAs (miRNAs) are a class of non-coding small RNAs that bind to target mRNAs, usually resulting in post-transcriptional repression by translational inhibition or target degradation. mRNAs can function as tumor suppressors or oncogenes (also referred to as oncomirs) in human tumors. Although aberrant expression of miR-335 has been reported in 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 17 normal ovarian tissues and 4 ovarian cancer cell lines using qPCR. We found that miR-335 was downregulated in the ovarian cancer cell lines relative to normal ovarian epithelium tissues. In vitro, overexpression of miR-335 suppressed cell migration and invasion and resulted in depolymerization of F-actin in ovarian cancer cell lines, but exhibited a negligible effect on cell proliferation. B-cell CLL/lymphoma 2 like 2 (Bcl-w or BCL2L2), a pro-survival member of the Bcl-2 protein family, was identified as a potential target of miR-335 according to the results of bioinformatic analysis, and the expression of Bcl-w and its effector matrix metalloproteinase-2 (MMP-2) was downregulated after transfection with miR-335 mimics. In addition, ectopic Bcl-w could almost fully nullify the effect of miR-335 overexpression on ovarian cancer cell migration and invasion. These findings indicate that the tiny genome product, miR-335, whose lack of expression brings about the abnormal accumulation of Bcl-w and subsequent unchecked cell invasion in ovarian cancer, may help us to understand one of the many steps ovarian cells take on their way toward the acquisition of malignant phenotypes and miR-335 may be a promising predictor of survival.