Tumor and Stem Cell Biology Survival in Patients with High-Risk Prostate Cancer Is Predicted by miR-221, Which Regulates Proliferation, Apoptosis, and InvasionofProstateCancerCells by Inhibiting IRF2 and SOCS3

A lack of reliably informative biomarkers to distinguish indolent and lethal prostate cancer is one reason this disease is overtreated. miR-221 has been suggested as a biomarker in high-risk prostate cancer, but there is insufficient evidence of its potential utility. Here we report that miR-221 is an independent predictor for cancerrelated death, extending and validating earlier findings. By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness, and apoptosis in prostate cancer at least partially via STAT1/STAT3-mediated activation of the JAK/STAT signaling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signaling pathway.miR-221 expression sensitized prostate cancer cells for IFN-g–mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk prostate cancer. Cancer Res; 74(9); 2591–603. 2014 AACR.