miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth.

Androgen Receptor (AR) mediated oncogenic pathways have not been fully elucidated. In this study we utilized high throughput microarray analysis on two AR-positive Prostate Cancer (CaP) cell lines to identify 16 AR-responsive microRNAs (miRNAs). We focused on miR-21 because of its previously reported oncogenic activity in other cancers. We demonstrate androgen-induced AR binding to the defined miR-21 promoter, miPPR-21, suggesting direct transcriptional regulation. Moreover, inhibition of miR-21 diminished androgen-induced CaP cell proliferation, providing new evidence that microRNAs can contribute to androgen-driven cell growth. Elevated expression of miR-21 enhanced CaP tumor growth in vivo and, surprisingly, was sufficient for androgen-dependent tumors to overcome castration-mediated growth arrest. Thus, elevated miR-21 expression alone is sufficient to impart castration resistance. Moreover, quantitative RT-PCR analysis revealed elevated miR-21 expression in CaP when compared to adjacent normal tissue. These results suggest that miR-21 may contribute to CaP pathogenesis.