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pre-miR-150(miR-150-5p 和 miR-150-3p)双链作为抗肿瘤 miRNA,靶向 naïve 和去势抵抗性前列腺癌中的 SPOCK1。

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.

机构信息

Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.

Department of Urology, Teikyo University Chiba Medical Center, Ichihara, Japan.

出版信息

Int J Oncol. 2017 Jul;51(1):245-256. doi: 10.3892/ijo.2017.4008. Epub 2017 May 17.

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.

摘要

我们对人类癌症中的 microRNA(miRNA)表达特征进行分析后发现,pre-miR-150 的引导链和 passenger 链,即 miR-150-5p 和 miR-150-3p,在癌症组织中明显下调。在 miRNA 生物发生过程中,miRNA 的 passenger 链被降解,被认为没有功能。因此,本研究旨在研究 miR-150-5p 和 miR-150-3p 在原代前列腺癌(PCa)和去势抵抗性前列腺癌(CRPC)中的功能意义。外源性表达实验表明,这两条 miRNA 链均显著抑制癌细胞的迁移和侵袭。我们的 miRNA 靶基因搜索策略表明,SPOCK1(SPARC/osteonectin,cwcv 和 kazal 样结构域蛋白聚糖 1)直接受 miR-150-5p 和 miR-150-3p 调控。siRNA 敲低 SPOCK1 抑制癌细胞侵袭。此外,在原代 PCa 和 CRPC 组织中观察到 SPOCK1 的过表达。总之,pre-miR-150 的双链(miR-150-5p 和 miR-150-3p)在原代 PCa 和 CRPC 细胞中作为抗肿瘤 miRNA 发挥作用。致癌 SPOCK1 的表达参与了原代 PCa 和 CRPC 的发病机制。对肿瘤抑制 miRNA 调控的 RNA 网络的分析可能为原代 PCa 和 CRPC 的发病机制提供新的见解。

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