Dual strands of pre-miR-150 (miR-150-5p and miR-150-3p) act as antitumor miRNAs targeting SPOCK1 in naive and castration-resistant prostate cancer

Analysis of our microRNA (miRNA) expression signature in human cancers has shown that guide and passenger strands of pre-miR-150, i.e., miR-150-5p and miR-150-3p, are significantly downregulated in cancer tissues. In miRNA biogenesis, the passenger strand of miRNA is degraded and is thought to have no functions. Thus, the aim of this study was to investigate the functional significance of miR-150-5p and miR-150-3p in naive prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). Ectopic expression assays showed that both strands of miRNAs significantly suppressed cancer cell migration and invasion. Our strategies of miRNA target searching demonstrated that SPOCK1 (SPARC/losteonectin, cwcv and kazal like domains proteoglycan 1) was directly regulated by miR-150-5p and miR-150-3p. Knockdown of SPOCK1 by siRNA inhibited cancer cell aggressiveness. Moreover, overexpression of SPOCK1 was observed in naive PCa and CRPC tissues. Taken together, dual strands of pre-miR-150 (miR-150-5p and miR-150-3p) acted as antitumor miRNAs in naive PCa and CRPC cells. Expression of oncogenic SPOCK1 was involved in naive PCa and CRPC pathogenesis. Novel approaches to analysis of antitumor miRNA-regulated RNA networks in cancer cells may provide new insights into the pathogenic mechanisms of naive PCa and CRPC.