MiR-3648 Promotes Prostate Cancer Cell Proliferation by Inhibiting Adenomatous Polyposis Coli 2.

Abstract

Prostate cancer is one of the most common malignancy among men, previous reports suggest that microRNA regulates prostate cancer progression. In present study, we found a novel miRNA, miR-3648, was to be overexpressed in prostate cancer tissues. Its overexpression promoted proliferation of the prostate cancer cell line, LNCaP, as determined by MTT, colony formation and soft agar growth assays. Consistently, knockdown of miR-3648 inhibited LNCaP proliferation. The tumor suppressor, adenomatous polyposis coli 2 (APC2), which negatively regulates the Wnt/β-catenin pathway, was the target of miR-3648. The results of the luciferase reporter assay suggested that miR-3648 binds directly to the 3'UTR of APC2. The Wnt/β-catenin pathway promotes G1/S transition. We evaluated whether miR-3648 regulated the expression of key regulatory proteins involved in G1/S transition, and found that miR-3648 promoted cyclin D1 and cyclin E1 expression while inhibiting p21 expression. This suggested that miR-3648 promoted LNCaP proliferation by targeting APC2, which in turn activates the Wnt/β-catenin pathway to produce the observed effects on cyclin D1, cyclin E1 and p21 expression. Moreover, there was a negative correlation between miR-3648 and APC2 expression in prostate cancer tissues.