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

Okato,Atsushi; Arai,Takayuki; Kojima,Satoko; Koshizuka,Keiichi; Osako,Yusaku; Idichi,Tetsuya; Kurozumi,Akira; Goto,Yusuke; Kato,Mayuko; Naya,Yukio; Ichikawa,Tomohiko; Seki,Naohiko

doi:10.3892/ijo.2017.4008

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

Authors:
- Atsushi Okato
- Takayuki Arai
- Satoko Kojima
- Keiichi Koshizuka
- Yusaku Osako
- Tetsuya Idichi
- Akira Kurozumi
- Yusuke Goto
- Mayuko Kato
- Yukio Naya
- Tomohiko Ichikawa
- Naohiko Seki
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Affiliations: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan, Department of Urology, Teikyo University Chiba Medical Center, Ichihara, Japan, Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan, Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan
Published online on: May 17, 2017 https://doi.org/10.3892/ijo.2017.4008
Pages: 245-256

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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 significance of miR‑150‑5p and miR‑150‑3p in naïve 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/osteonectin, 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 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.

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