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
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
复制标题
DOI：
10.3892/ijo.2017.4008
复制
发表时间：
2017-07-01
影响因子：
5.2
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
--
作者：
Okato, Atsushi;Arai, Takayuki;Seki, Naohiko
我们对人类癌症中microRNA（miRNA）表达特征的分析表明，前体miR-150的引导链和过客链，即，miR-150- 5 p和miR-150- 3 p在癌组织中显著下调。在miRNA生物发生中，miRNA的过客链被降解，被认为没有功能。因此，本研究的目的是研究miR-150- 5 p和miR-150- 3 p在幼稚前列腺癌（PCa）和去势抵抗性前列腺癌（CRPC）中的功能意义。异位表达分析表明，两条链的miRNAs显着抑制癌细胞的迁移和侵袭。我们的miRNA靶点搜索策略表明，SPOCK 1（p53/losteonectin，cwcv and kazal like domains proteoglycan 1）受miR-150- 5 p和miR-150- 3 p的直接调控。通过siRNA敲低SPOCK 1可抑制癌细胞的侵袭性。此外，在初始PCa和CRPC组织中观察到SPOCK 1的过表达。总之，前体miR-150的双链（miR-150- 5 p和miR-150- 3 p）在初始PCa和CRPC细胞中充当抗肿瘤miRNA。致癌基因SPOCK 1的表达参与了原发性PCa和CRPC的发病机制。分析癌细胞中抗肿瘤miRNA调控的RNA网络的新方法可能为幼稚PCa和CRPC的致病机制提供新的见解。
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.