Systematic Analysis of MicroRNAs Targeting the Androgen Receptor in Prostate Cancer Cells.

摘要: Androgen receptor (AR) is expressed in all stages of prostate cancer progression, including castration-resistant tumors. Eliminating AR function continues to represent a focus therapeutic investigation, but regulatory mechanisms remain poorly understood. To systematically characterize involving microRNAs (miRNAs), we conducted gain-of screen 1129 miRNA molecules panel human cell lines and quantified changes protein content using lysate microarrays. In this way, defined 71 unique miRNAs that influenced the level cells. RNA sequencing data revealed 3'UTR (and other genes) much longer than currently used target prediction programs. Our own analyses predicted most regulation would an extended 6 kb 3'UTR. 3'UTR-binding assays validated 13 are able regulate long (miR-135b, miR-185, miR-297, miR-299-3p, miR-34a, miR-34c, miR-371-3p, miR-421, miR-449a, miR-449b, miR-634, miR-654-5p, miR-9). Fifteen downregulating decreased androgen-induced proliferation particular, analysis clinical cancers confirmed negative correlation miR-34a miR-34c expression with levels. findings establish interacting gene important regulators levels, implications for developing new strategies inhibit androgen-dependent growth.