Zhao Xinmin, Shen Lei, Feng Yu, Yu Hui, Wu Xianghua, Chang Jianhua, Shen Xuxia, Qiao Jie, Wang Jialei
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Tumour Biol. 2015 Sep;36(9):6733-40. doi: 10.1007/s13277-015-3371-9. Epub 2015 Apr 3.
Lung cancer is the leading cause of cancer-related death in the world. Previous report has identified ribosomal protein s15a (RPS15A) as a TGF-β-responsible gene in the lung adenocarcinoma cell line A549. In this study, we used specific si-RNA to downregulate RPS15A expression in A549 cells and found that decreased RPS15A expression significantly inhibited cell proliferation and survival, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Moreover, A549 cells were obviously accumulated in the G0/G1 phase in response to RPS15A knockdown, suggesting that RPS15A inhibition could induce a diminution of proliferation through cell cycle arrest. In addition, immunohistochemistry analysis further revealed that RPS15A was overexpressed in surgically resected lung cancer tissues. In conclusion, we identify RPS15A as a novel potential oncogenic gene involved in lung carcinogenesis. This study may provide a preliminary experimental basis for a gene therapy approach for treating lung cancer.
肺癌是全球癌症相关死亡的主要原因。先前的报告已确定核糖体蛋白s15a(RPS15A)是肺腺癌细胞系A549中一种受转化生长因子-β(TGF-β)调控的基因。在本研究中,我们使用特异性小干扰RNA(si-RNA)下调A549细胞中RPS15A的表达,并且通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)和集落形成试验发现,RPS15A表达降低显著抑制细胞增殖和存活。此外,响应于RPS15A敲低,A549细胞明显积聚在G0/G1期,这表明抑制RPS15A可通过细胞周期停滞诱导增殖减少。另外,免疫组织化学分析进一步显示,RPS15A在手术切除的肺癌组织中过表达。总之,我们确定RPS15A是一种参与肺癌发生的新型潜在致癌基因。本研究可能为肺癌的基因治疗方法提供初步实验依据。