MicroRNA-135a induces prostate cancer cell apoptosis via inhibition of STAT6.

Abstract

Clinical management of metastatic prostate cancer remains a challenge. Activation of apoptosis signaling pathways via signal transducer and activator of transcription 6 (STAT6) has been hypothesized to be a therapeutic strategy for patients with metastatic prostate cancer. The ONCOMINE® prostate cancer database and two Gene Expression Omnibus datasets (Gene Series 40026 and 21032) were re-analyzed to determine the expression levels of STAT6 and microRNA (miR)-135a in prostate cancer. The current study investigated the induced overexpression of miR-135a in prostate cancer cell lines to detect its function in prostate cell apoptosis using Hoechst staining and fluorescence-activated cell sorting and examined the expression levels of STAT6 and its DNA binding ability using western blotting and an electrophoretic mobility shift assay. In analysis of the ONCOMINE® database, STAT6 expression levels in prostate cancer tissue were higher compared with those in normal prostate gland tissue and were associated with the overall survival rate and biochemical relapse rate following radical prostatectomy. Additionally, there was an inverse correlation between miR-135a and STAT6 expression levels in prostate cancer cell lines. miR-135a was able to induce prostate cancer cell apoptosis via targeting STAT6 mRNA and subsequently repressing protein expression and phosphorylation, which also altered the transcriptional factor function of STAT6 through its DNA-binding capabilities. In conclusion, miR-135a may function as a tumor-suppressing miRNA in prostate cancer and its anti-oncogenic activity may involve the direct targeting and inhibition of STAT6.