Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C
Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C
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DOI：
10.1038/jhg.2014.111
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发表时间：
2015-02-01
影响因子：
3.5
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
--
作者：
Mataki, Hiroko;Enokida, Hideki;Seki, Naohiko
肺癌显然是全世界癌症相关死亡的主要原因。最近的分子靶向策略有助于提高肺腺癌的疗效。然而，目前尚未开发出针对鳞状细胞癌（SCC）疾病的此类治疗方法。肺鳞状细胞癌的新全基因组RNA分析可能为该疾病的研究和发展提供新途径。我们最近的肺鳞状细胞癌的 microRNA (miRNA) 表达特征表明，癌症组织中聚集的 miRNA miR-1/133a 显着减少。在这里，我们发现成熟 miR-1 和 miR-133a 的恢复显着抑制癌细胞增殖、迁移和侵袭。全基因组基因表达分析和荧光素酶报告基因检测显示，Coronin-1C (CORO1C) 是 miR-1/133a 簇的常见靶基因。 CORO1C基因表达沉默可抑制癌细胞增殖、迁移和侵袭。此外，通过使用si-CORO1C转染子对CORO1C调节的分子途径进行了分类。对肿瘤抑制簇 miR-1/133a 调节的新型癌症信号通路的进一步分析将为了解肺鳞状细胞癌肿瘤发生和转移的分子机制提供见解。
Lung cancer is clearly the primary cause of cancer-related deaths worldwide. Recent molecular-targeted strategy has contributed to improvement of the curative effect of adenocarcinoma of the lung. However, such current treatment has not been developed for squamous cell carcinoma (SCC) of the disease. The new genome-wide RNA analysis of lung-SCC may provide new avenues for research and the development of the disease. Our recent microRNA (miRNA) expression signatures of lung-SCC revealed that clustered miRNAs miR-1/133a were significantly reduced in cancer tissues. Here, we found that restoration of both mature miR-1 and miR-133a significantly inhibited cancer cell proliferation, migration and invasion. Coronin-1C (CORO1C) was a common target gene of the miR-1/133a cluster, as shown by the genome-wide gene expression analysis and the luciferase reporter assay. Silencing of CORO1C gene expression inhibited cancer cell proliferation, migration and invasion. Furthermore, CORO1C-regulated molecular pathways were categorized by using si-CORO1C transfectants. Further analysis of novel cancer signaling pathways modulated by the tumor-suppressive cluster miR-1/133a will provide insights into the molecular mechanisms of lung-SCC oncogenesis and metastasis.