Wu Xiaobin, Liu Wei, Liu Xueliang, Ai Qing, Yu Jialin
Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People's Republic of China.
Onco Targets Ther. 2018 May 25;11:3111-3117. doi: 10.2147/OTT.S156102. eCollection 2018.
The role of dysfunction of , a recently identified tumor suppressor gene, has not yet been established in lung cancer. In our previous study, it was reported that expression is downregulated in lung cancer tissues and that overexpression inhibits the proliferation of non-small-cell lung cancer cells. The results can be found in the APJC and journals.
Kaplan-Meier survival analysis was conducted to explore the prognostic significance of MCPH1. Cell experiments were performed to investigate the effects of MCPH1 on the biologic behaviors of lung cancer cells.
In the current study, microarray analysis of MCPH1 revealed that lung cancer patients with high MCPH1 expression had longer relapse-free survival. Overexpression of MCPH1 in A549 lung carcinoma cells successfully inhibited cell migration and invasion. Moreover, overexpression of MCPH1 inhibited migration and invasion by regulating the activities of several proteins that control the epithelial-mesenchymal transition, such as Slug, Snail, E-cadherin, Mdm2, and p53.
Our results indicate that downregulation of MCPH1 correlates with tumor progression in lung cancer, and hence MCPH1 may be an important tumor suppressor gene and a novel candidate therapeutic target in lung cancer.
最近发现的肿瘤抑制基因MCPH1功能障碍在肺癌中的作用尚未明确。在我们之前的研究中,据报道MCPH1在肺癌组织中的表达下调,且MCPH1过表达抑制非小细胞肺癌细胞的增殖。相关结果发表于《亚太癌症预防杂志》和其他期刊。
进行Kaplan-Meier生存分析以探讨MCPH1的预后意义。开展细胞实验以研究MCPH1对肺癌细胞生物学行为的影响。
在本研究中,对MCPH1的微阵列分析显示,MCPH1高表达的肺癌患者无复发生存期更长。在A549肺癌细胞中过表达MCPH1成功抑制了细胞迁移和侵袭。此外,MCPH1过表达通过调节几种控制上皮-间质转化的蛋白(如Slug、Snail、E-钙黏蛋白、Mdm2和p53)的活性来抑制迁移和侵袭。
我们的结果表明,MCPH1下调与肺癌肿瘤进展相关,因此MCPH1可能是肺癌中一个重要的肿瘤抑制基因和新的候选治疗靶点。