MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker.
MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker.
复制标题
耐法前列腺癌的microRNA表达特征：microRNA-221/222簇作为肿瘤抑制剂和疾病进展标记物的作用。
DOI：
10.1038/bjc.2015.300
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发表时间：
2015-09-29
影响因子：
8.8
通讯作者：
Seki N
中科院分区：
文献类型：
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作者：
Goto Y;Kojima S;Nishikawa R;Kurozumi A;Kato M;Enokida H;Matsushita R;Yamazaki K;Ishida Y;Nakagawa M;Naya Y;Ichikawa T;Seki N
我们目前对去势抵抗性前列腺癌（CRPC）中microRNA（miRNA）表达特征的研究表明，成簇的miRNA microRNA-221（miR-221）和microRNA-222（miR-222）在癌组织中显著下调。本研究旨在探讨miR-221和miR-222在前列腺癌细胞中的功能作用。通过基于PCR的阵列方法构建CRPC miRNA标签。使用PCa细胞分析差异表达的miRNA的功能研究。通过Kaplan-Meier方法估计miRNA表达与总生存期之间的关联。进行计算机数据库和全基因组基因表达分析以鉴定由miR-221/222簇调控的分子靶标。miR-221和miR-222在PCa和CRPC标本中显著下调。Kaplan-Meier生存曲线显示，miR-222的低表达预示着进展为CRPC的持续时间较短。在癌细胞中恢复miR-221或miR-222揭示了这两种miRNA显著抑制癌细胞迁移和侵袭。在PCa细胞中，Ecm 29直接受miR-221/222簇的调控。肿瘤抑制性miR-221/222簇的丢失增强了PCa细胞的迁移和侵袭。我们的数据描述了由肿瘤抑制性miR-221/222簇调控的靶点，为PCa和CRPC进展的机制提供了见解。
Our present study of the microRNA (miRNA) expression signature in castration-resistant prostate cancer (CRPC) revealed that the clustered miRNAs microRNA-221 (miR-221) and microRNA-222 (miR-222) are significantly downregulated in cancer tissues. The aim of this study was to investigate the functional roles of miR-221 and miR-222 in prostate cancer (PCa) cells. A CRPC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were analysed using PCa cells. The association between miRNA expression and overall survival was estimated by the Kaplan–Meier method. In silico database and genome-wide gene expression analyses were performed to identify molecular targets regulated by the miR-221/222 cluster. miR-221 and miR-222 were significantly downregulated in PCa and CRPC specimens. Kaplan–Meier survival curves showed that low expression of miR-222 predicted a short duration of progression to CRPC. Restoration of miR-221 or miR-222 in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Ecm29 was directly regulated by the miR-221/222 cluster in PCa cells. Loss of the tumour-suppressive miR-221/222 cluster enhanced migration and invasion in PCa cells. Our data describing targets regulated by the tumour-suppressive miR-221/222 cluster provide insights into the mechanisms of PCa and CRPC progression.