Targeted p21 activation by a new double stranded RNA suppresses human prostate cancer cells growth and metastasis.

We have previously demonstrated that miR-1236-3p and its sequence homology dsRNA, dsRNA-245 (which is completely complementary to the p21 promoter) had potential ability to upregulate p21 expression by targeting specific promoter sequence and inhibited bladder cancer (BCa). However, we still know little about the effect of miR-1236-3p on prostate cancer and which dsRNA has an inhibitory effect on prostate cancer (PCa)? Here, we confirmed that miR-1236-3p was decreased in PCa cells and tissues. MiR-1236-3p inhibited PCa cells growth and metastasis by activating p21. Furthermore, we demonstrated that dsP21-245 could inhibit PCa cells growth and metastasis by activating p21 expression. Microarray experiments displayed that miR-1236-3p could affect AKT signaling pathway. We demonstrated that miR-1236-3p significantly suppressed the AKT pathway by inhibiting TLR2 expression while activating p21 expression in PCa cells; this influence was independent of p21 activation. In summary, our results provided evidence that both endogenous and exogenous small RNAs might function to induce p21 expression by interacting with the same promoter region, therefore impeding PCa development. Additionally, our results indicated that miRNA activation could activate the expression of some unknown genes as well as cell signaling pathways. This indicated the need for the further study of clinical applications of RNA activation.