miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1

ABSTRACT BACKGROUND miR‐146a (miR‐146a‐5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR‐146a in prostate cancer is still limited. METHODS The expression levels of miR‐146a in cell lines and tissues were measured by qRT‐PCR and in situ hybridization. Effects of miR‐146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR‐146a and the 3'UTR of potential targets. RESULTS We found that enforced over‐expression of miR‐146a in prostate cancer cells suppressed whereas knockdown of miR‐146a increased anchorage‐independent growth, migration, and invasion. Mechanistic studies revealed that miR‐146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti‐migration effect of overexpressing miR‐146a, and knockdown of Rac1 in miR‐146a‐silencing cells antagonized the increase in cell motility induced by silencing miR‐146a. Furthermore, miR‐146a was found to be inversely correlated with Rac1 in human prostate cancer tissues. CONCLUSIONS Our data suggest that miR‐146a plays a suppressive role in prostate cancer through down‐regulation of Rac1. The miR‐146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression. Prostate 74: 1613–1621, 2014. © 2014 Wiley Periodicals, Inc.