Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.
Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.
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DOI：
10.1111/cas.12842
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发表时间：
2016-01
期刊：
影响因子：
5.7
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Kurozumi A;Goto Y;Matsushita R;Fukumoto I;Kato M;Nishikawa R;Sakamoto S;Enokida H;Nakagawa M;Ichikawa T;Seki N
对前列腺癌 (PCa) 和去势抵抗性 PCa 中 microRNA (miRNA) 表达特征的分析表明，miRNA-223 在癌症组织中显着下调，表明 miR-223 通过靶向癌基因发挥肿瘤抑制 miRNA 的作用。本研究的目的是研究 miR-223 的功能作用并确定 miR-223 在 PCa 细胞中调节的下游致癌靶点。使用 PC3 和 PC3M PCa 细胞系进行 miR-223 的功能研究，以研究细胞增殖、迁移和侵袭。 miR-223 的恢复显着抑制 PCa 细胞中的癌细胞迁移和侵袭。计算机数据库和全基因组基因表达分析表明，ITGA3 和 ITGB1 是 miR-223 调控的直接靶标。 ITGA3 和 ITGB1 的敲低通过调节下游信号传导显着抑制 PCa 细胞中的癌细胞迁移和侵袭。此外，在 PCa 临床标本中观察到 ITGA3 和 ITGB1 的过度表达。因此，我们的数据表明，miR-223 的下调增强了 ITGA3/ITGB1 信号传导，并有助于 PCa 细胞中癌细胞的迁移和侵袭。阐明肿瘤抑制 miRNA 调节的分子途径有助于深入了解 PCa 进展和转移的机制。
Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration‐resistant PCa has revealed that miRNA‐223 is significantly downregulated in cancer tissues, suggesting that miR‐223 acts as a tumor‐suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR‐223 and identify downstream oncogenic targets regulated by miR‐223 in PCa cells. Functional studies of miR‐223 were carried out to investigate cell proliferation, migration, and invasion using PC3 and PC3M PCa cell lines. Restoration of miR‐223 significantly inhibited cancer cell migration and invasion in PCa cells. In silico database and genome‐wide gene expression analyses revealed that ITGA3 and ITGB1 were direct targets of miR‐223 regulation. Knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion in PCa cells by regulating downstream signaling. Moreover, overexpression of ITGA3 and ITGB1 was observed in PCa clinical specimens. Thus, our data indicated that downregulation of miR‐223 enhanced ITGA3/ITGB1 signaling and contributed to cancer cell migration and invasion in PCa cells. Elucidation of the molecular pathways modulated by tumor‐suppressive miRNAs provides insights into the mechanisms of PCa progression and metastasis.