An androgen-regulated miR-2909 modulates TGFβ signalling through AR/miR-2909 axis in prostate cancer

In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for PCa diagnosis and prognosis. miR-2909 is a novel miRNA that can regulate immunogenomics and oncogenomics. The present study investigated the role of miR-2909 in the pathogenesis of PCa and the potential signalling pathways through which it operates. We have identified miR-2909 as a novel mediator of androgen/androgen receptor (AR) signalling that enhances the proliferation potential of PCa cells and assists in cancer survival under reduced androgen levels. Our results revealed that miR-2909 down regulates TGFBR2 by targeting its 3'-UTR sequence. We also observed that miR-2909 over-expression attenuated TGFβ-mediated SMAD3 activation, cell growth inhibition and apoptosis. Moreover, miR-2909 modulated the expression of p21CIP, c-MYC and CCND1 through TGFβ signalling. Importantly, we also demonstrated that miR-2909 and AR regulates each other's expression resulting in a positive feedback loop. In conclusion, our study suggests that miR-2909 is an androgen-inducible miRNA that exerts its oncogenic effects by attenuating the tumor-suppressive effects of TGFβ signalling.