MicroRNA-9-5p functions as a tumor suppressor in prostate cancer via targeting UTRN

Abstract

Accumulating evidence indicates that miR-9-5p plays an important role in several diseases, especially tumor progression. In this study, we investigated the clinical significance and biological function of miR-9-5p in prostate cancer (PCa). Using quantitative real time PCR (qRT-PCR) analysis, we found miR-9-5p level was significantly down-regulated in PCa tissues and cell lines. The decreased miR-9-5p expression was associated with tumor size, preoperative PSA, Gleason score and lymph node metastasis. Kaplan-Meier survival analysis showed patients with low level of miR-9-5p had significantly decreased rates of overall survival (OS). Multivariate analyses showed that miR-9-5p was an independent predictor of PCa patients’ prognosis. Through CCK-8 and Transwell assays, miR-9-5p overexpression by miR-9-5p mimics transfection was demonstrated to suppress the proliferation, migration and invasion of PCa cells. Mechanistically, luciferase reporter assay, qRT-PCR and Western blot demonstrated that Utrophin (UTRN) is a direct target of miR-9-5p in PCa cells. The status of UTRN protein in PCa tissues was much higher than that in adjacent tissues by immunohistochemical staining and its mRNA levels were inversely correlated with miR-9-5p in PCa tissues. Importantly, UTRN knockdown by siUTRN imitated the suppressive effects of miR-9-5p on cell proliferation, migration and invasion in PCa. In summary, miR-9-5p might novel prognostic biomarker in and targeting UTRN by miR-9-5p could be potential therapeutic candidates for PCa.