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鉴定微小RNA-615-3p为非小细胞肺癌中的一种新型肿瘤抑制因子。

Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer.

作者信息

Pu Heng-Ying, Xu Rui, Zhang Mei-Yin, Yuan Lin-Jing, Hu Jing-Ye, Huang Guo-Liang, Wang Hui-Yun

机构信息

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.

Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.

出版信息

Oncol Lett. 2017 Apr;13(4):2403-2410. doi: 10.3892/ol.2017.5684. Epub 2017 Feb 7.

Abstract

Lung cancer is the most frequent cause of mortality in cancer patients; non-small-cell lung cancer (NSCLC) accounts for ~80% of lung cancer cases. MicroRNAs (miRNAs) have been revealed to perform an important role in cancer development and progression. Based on a custom miRNA microarray analysis of patients with NSCLC, miRNA-615-3p (miR-615-3p) downregulation was identified in NSCLC tissues compared with normal lung tissues, which suggested that miR-615-3p acted as a tumor suppressor in lung cancer. The overexpression of miR-615-3p was then validated using 40 pairs of NSCLC and adjacent normal tissue samples using a TaqMan reverse transcription-quantitative polymerase chain reaction assay. In order to investigate the tumor suppressor function of miR-615-3p, the ectopic expression of miR-615-3p in the NSCLC A549, H1299 and H1650 cell lines was established. The results revealed that overexpressed miR-615-3p markedly inhibited cell proliferation and colony formation in the 3 NSCLC cell lines compared with the cells overexpressing the negative control sequence (NC). Additional investigation revealed that miR-615-3p overexpression significantly induced apoptosis and cell cycle arrest at the G1 phase in the A549, H1299 and H1650 cell lines compared with the cells overexpressing NC. Finally, ectopic expression of miR-615-3p was found to repress the cell migration and invasion of the 3 lung cancer cell lines. The results of the present study demonstrate, for the first time, that miR-615-3p functions as a tumor suppressor in NSCLC, and may be a novel potential molecular therapeutic target for patients with NSCLC.

摘要

肺癌是癌症患者最常见的死亡原因;非小细胞肺癌(NSCLC)约占肺癌病例的80%。微小RNA(miRNA)已被证明在癌症发生和发展中起重要作用。基于对NSCLC患者的定制miRNA微阵列分析,与正常肺组织相比,NSCLC组织中miRNA-615-3p(miR-615-3p)表达下调,这表明miR-615-3p在肺癌中起肿瘤抑制作用。然后使用TaqMan逆转录定量聚合酶链反应测定法,在40对NSCLC及其相邻正常组织样本中验证了miR-615-3p的过表达。为了研究miR-615-3p的肿瘤抑制功能,在NSCLC A549、H1299和H1650细胞系中建立了miR-615-3p的异位表达。结果显示,与过表达阴性对照序列(NC)的细胞相比,过表达的miR-615-3p显著抑制了3种NSCLC细胞系中的细胞增殖和集落形成。进一步研究发现,与过表达NC的细胞相比,miR-615-3p过表达显著诱导了A549、H1299和H1650细胞系中的细胞凋亡并使细胞周期停滞在G1期。最后,发现miR-615-3p的异位表达抑制了3种肺癌细胞系的细胞迁移和侵袭。本研究结果首次证明,miR-615-3p在NSCLC中起肿瘤抑制作用,可能是NSCLC患者新的潜在分子治疗靶点。

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