MiR-182 promotes prostate cancer progression through activating Wnt/β-catenin signal pathway

Although prostate cancer can be surgical excised and effectively treated by androgen-deprivation therapy, radiotherapy, or chemotherapy, management of patients with advanced or drug-resistance prostate cancer stills remains a big trouble. Accumulated evidence indicated that miR-182 and Wnt/beta-catenin function as tumor oncogene in the progression of a variety of tumors. However, little is known about how miR-182 regulates beta-catenin signal molecular and impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of qRT-PCR, we found that prostate cancer tissues expressed much more miR-182 than non-cancer tissues did. In vitro studies revealed that overexpression of miR-182 promoted cell proliferation, colony formation, migration, invasion and inhibited cell apoptosis; in vivo results demonstrated that silencing of miR-182 mediated by inhibitor dramatically reduced prostate cancer xenograft tumor growth. Importantly, through western blotting analysis, we identified that miR-182 dramatically activated Wnt/beta-catenin pathway by targeting multiple negative regulators of Wnt/beta-catenin signaling, including GSK-3 beta, APC, CK1 and Axin. Besides, we observed the elevated levels of c-myc and Cyclin D1 when PC-3 and LNCap cells were up-regulated miR-182. Our findings indicate that miR-182 acts as one of oncogenic factor in the progression of prostate cancer by recruiting a mechanism of aberrant activation of Wnt/beta-catenin signaling.