Mataki Hiroko, Enokida Hideki, Chiyomaru Takeshi, Mizuno Keiko, Matsushita Ryosuke, Goto Yusuke, Nishikawa Rika, Higashimoto Ikkou, Samukawa Takuya, Nakagawa Masayuki, Inoue Hiromasa, Seki Naohiko
Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
J Hum Genet. 2015 Feb;60(2):53-61. doi: 10.1038/jhg.2014.111. Epub 2014 Dec 18.
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.
肺癌显然是全球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治疗效果。然而，目前尚未针对该疾病的鳞状细胞癌（SCC）开发出此类治疗方法。对肺SCC进行的全基因组RNA分析可能为该疾病的研究和开发提供新途径。我们最近对肺SCC的微小RNA（miRNA）表达特征分析显示，成簇的miRNA miR-1/133a在癌组织中显著减少。在此，我们发现成熟的miR-1和miR-133a的恢复均能显著抑制癌细胞的增殖、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表明，冠蛋白-1C（CORO1C）是miR-1/133a簇的共同靶基因。CORO1C基因表达的沉默抑制了癌细胞的增殖、迁移和侵袭。此外，通过使用si-CORO1C转染细胞对CORO1C调节的分子途径进行了分类。对由肿瘤抑制性簇miR-1/133a调节的新型癌症信号通路的进一步分析将为肺SCC发生和转移的分子机制提供见解。
