Micro-ribonucleic acid expression signature of metastatic castration-resistant prostate cancer: Regulation of NCAPH by antitumor miR-199a/b-3p.

Abstract

To identify oncogenes regulated by micro-ribonucleic acid, miR-199a/b-3p, in metastatic castration-resistant prostate cancer. Advanced ribonucleic acid sequencing technologies were applied to construct a micro-ribonucleic acid expression signature using metastatic castration-resistant prostate cancer autopsy specimens. Ectopic expression of mature micro-ribonucleic acids or small-interfering ribonucleic acids were applied to functional assays for cancer cell lines. Genome-wide gene expression and insilico database analyses were carried out to predict micro-ribonucleic acid targets. Ectopic expression of miR-199a/b inhibited cancer cell aggressiveness. The gene coding for non-structural maintenance of chromosomes condensinI complex subunitH was directly regulated by miR-199a/b-3p. High expression of condensinI complex subunitH was significantly associated with poor disease-free survival by The Cancer Genome Atlas database analysis (P<0.0001). Overexpression of condensinI complex subunitH was detected in hormone-sensitive prostate cancer and castration-resistant prostate cancer specimens, and knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities. Small ribonucleic acid sequencing of metastatic castration-resistant prostate cancer specimens showed the presence of several antitumor micro-ribonucleic acids whose targets are involved in hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer pathogenesis. CondensinI complex subunitH seems to be a promising diagnostic marker and therapeutic target for this disease. Our approach, based on the roles of anti-tumor micro-ribonucleic acids and their targets, will contribute to an improved understanding of the molecular pathogenesis of hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer.