MiR-5195-3p Functions as a Tumor Suppressor in Prostate Cancer via Targeting CCNL1

Abstract

BackgroundAccumulating evidence indicates miR-5195-3p exerts tumor suppressive role in several tumors. However, there is limited research on the clinical significance and biological function of miR-5195-3p in prostate cancer (PCa).MethodsExpression levels of miR-5195-3p and Cyclin L1 (CCNL1) were determined using quantitative real-time PCR. The clinical significance of miR-5195-3p in PCa patients was evaluated using Kaplan-Meier survival analysis and Cox regression models. Cell proliferation and cell cycle distribution were measured by CCK-8 assay and flow cytometry, respectively. The association between miR-5195-3p and CCNL1 was analyzed by luciferase reporter assay.ResultsMiR-5195-3p expression levels were significantly downregulated in 69 paired PCa tissues compared with matched adjacent normal tissues. The decreased miR-5195-3p expression was associated with Gleason score and TNM stage, as well as worse survival prognosis. The in vitro experiments showed that miR-5195-3p overexpression suppressed the proliferation and cell cycle G1/S transition in PC-3 and DU145 cells. Elevated miR-5195-3p abundance was also demonstrated to impair tumor formation in vivo using PC-3 xenografts. Mechanistically, Cyclin L1 (CCNL1) was a direct target of miR-5195-3p in PCa cells, which was inversely correlated with miR-5195-3p in PCa tissues. Importantly, CCNL1 knockdown imitated, while overexpression reversed the effects of miR-5195-3p overexpression on PCa cell proliferation and cell cycle G1/S transition.ConclusionsOur data suggests that miR-5195-3p functions as a tumor suppressor via downregulating G1/S related CCNL1 expression in PCa.