INTERNATIONAL JOURNAL OF ONCOLOGY 51: 245-256, 2017 Abstract. 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 signifcance of miR‑150‑5p and miR‑150‑3p in naïve prostate cancer (PCa) and castration-resis- tant prostate cancer (CRPC). Ectopic expression assays showed that both strands of miRNAs signifcantly suppressed cancer cell migration and invasion. Our strategies of miRNA target searching demonstrated that SPOCK1 (SPARC/osteonectin, cwcv and kazal like domains proteoglycan 1) was directly regu- lated by miR‑150‑5p and miR‑150‑3p . Knockdown of SPOCK1 by siRNA inhibited cancer cell aggressiveness. Moreover, overexpression of SPOCK1 was observed in naïve PCa and CRPC tissues. Taken together, dual strands of pre-miR‑150 ( miR‑150‑5p and miR‑150‑3p ) acted as antitumor miRNAs in naïve PCa and CRPC cells. Expression of oncogenic SPOCK1 was involved in naïve 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 naïve PCa and CRPC. Introduction Prostate cancer (PCa) is the most frequently diagnosed cancer among men in developed countries (1). Although PCa is initially responsive to androgen-deprivation therapy (ADT), most patients experience disease relapse and develop castra- tion-resistant prostate cancer (CRPC) (2). The survival rate of patients with CRPC is poor owing to the occurrence of metastasis (3) and patients with metastatic CRPC cannot be effectively treated using recently developed molecular-targeted therapies (2,3). Therefore, new treatment strategies are needed for these patients. The molecular mechanisms underlying the aggressiveness of CRPC cells and the acquisition of treatment resistance are still unclear. MicroRNAs (miRNAs) are noncoding RNAs that act as sequence-specifc fne tuners for regulating the expression levels of proteins and RNAs (4,5). Notably, a single miRNA can regulate a large number of RNA transcripts in human cells (6). Accordingly, dysregulation of miRNAs can disrupt the tightly regulated RNA networks in cancer cells, leading to cancer cell initiation, development, metastasis, and drug resistance (7,8). The discovery of miRNAs has complicated the analysis of intracellular RNA networks in cancer. We recently constructed an RNA-sequence based miRNA expression signature using autopsy specimens from patients with CRPC (9). To elucidate the miRNA-mediated RNA networks in metastatic CRPC, we have sequentially identifed antitumor miRNAs and oncogenic genes regulated by these miRNAs based on our miRNA expression signatures (9,10). Analysis of our miRNA signatures, including that in CRPC, has shown that both strands of pre-miR‑150, i.e., miR‑150‑5p (the guide strand) and miR‑150‑3p (the passenger strand), are signifcantly reduced in cancer tissues (9). In miRNA biogenesis, pre-miRNA is cleaved by Dicer into the miRNA duplex, containing the guide and passenger strands. The mature guide strand miRNA is incorporated into the RNA-induced silencing complex (RISC) and represses mRNA translation or cleaves mRNA (11). In contrast, the passenger strand of miRNA was previously thought to be degraded and to have no function (12-14). However, our expression data have contradicted this established miRNA theory. We hypothesized that the passenger strand of miR‑150‑3p may have functions in naïve PCa and CRPC cells by targeting novel oncogenic Dual strands of pre-miR‑150 (miR‑150‑5p and miR‑150‑3p) act as antitumor miRNAs targeting SPOCK1 in naïve and castration-resistant prostate cancer ATSUSHI OKATO 1,2 , TAKAYUKI ARAI 1,2 , SATOKO KOJIMA 3 , KEIICHI KOSHIzUKA 1 , YUSAKU OSAKO 4 , TETSUYA IDICHI 4 , AKIRA KUROzUMI 1,2 , YUSUKE GOTO 1,2 , MAYUKO KATO 1,2 , YUKIO NAYA 3 , TOMOHIKO ICHIKAWA 2 and NAOHIKO SEKI 1 Departments of 1 Functional Genomics and 2 Urology, Chiba University Graduate School of Medicine, Chiba; 3 Department of Urology, Teikyo University Chiba Medical Center, Ichihara; 4 Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan Received March 7, 2017; Accepted April 21, 2017 DOI: 10.3892/ijo.2017.4008 Correspondence to: Dr Naohiko Seki, Department of Functional Genomics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan E-mail: naoseki@faculty.chiba-u.jp Key words: microRNA, miR‑150‑5p, miR‑150‑3p, prostate cancer, castration-resistant prostate cancer, SPOCK