Goto Yusuke, Kojima Satoko, Nishikawa Rika, Enokida Hideki, Chiyomaru Takeshi, Kinoshita Takashi, Nakagawa Masayuki, Naya Yukio, Ichikawa Tomohiko, Seki Naohiko
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan. Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan.
Oncotarget. 2014 Sep 15;5(17):7748-59. doi: 10.18632/oncotarget.2294.
Our recent study of microRNA (miRNA) expression signatures in prostate cancer (PCa) has revealed that all members of the miR-23b/27b/24-1 cluster are significantly downregulated in PCa tissues. The aim of this study was to investigate the effectiveness of these clustered miRNAs as a disease progression marker and to determine the functional significance of these clustered miRNAs in PCa. Expression of the miR-23b/27b/24-1 cluster was significantly reduced in PCa tissues. Kaplan-Meier survival curves showed that low expression of miR-27b predicted a short duration of progression to castration-resistant PCa. Gain-of-function studies using mature miR-23b, miR-27b,and miR-24-1 significantly inhibited cell proliferation, migration and invasion in PCa cells (PC3 and DU145). To identify the molecular targets of these miRNAs, we carried out gene expression and in silico database analyses. GOLM1 was directly regulated by miR-27b in PCa cells. Elucidation of the molecular targets and pathways regulated by the tumor-suppressive microRNAs should shed light on the oncogenic and metastatic processes in PCa.
我们最近对前列腺癌(PCa)中微小RNA(miRNA)表达特征的研究表明,miR-23b/27b/24-1簇的所有成员在PCa组织中均显著下调。本研究的目的是调查这些成簇miRNA作为疾病进展标志物的有效性,并确定这些成簇miRNA在PCa中的功能意义。miR-23b/27b/24-1簇在PCa组织中的表达显著降低。Kaplan-Meier生存曲线显示,miR-27b低表达预示着去势抵抗性PCa进展时间短。使用成熟的miR-23b、miR-27b和miR-24-1进行的功能获得性研究显著抑制了PCa细胞(PC3和DU145)的细胞增殖、迁移和侵袭。为了鉴定这些miRNA的分子靶点,我们进行了基因表达和计算机数据库分析。在PCa细胞中,GOLM1受miR-27b直接调控。阐明肿瘤抑制性微小RNA调控的分子靶点和途径应有助于揭示PCa的致癌和转移过程。