Stomatin plays a suppressor role in non-small cell lung cancer metastasis

作     者：Huaying An Xiao Ma Mingyi Liu Xiaotong Wang Xundong Wei Wei Yuan Jie Ma 

作者机构：State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Center of BiotherapyBeijing HospitalNational Center of Gerontology/Institute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2019年第31卷第6期

页      面：930-944页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (No. 81602576, 81802872) National Key Research and Development Program of China (No. 2016YFA0201503) Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (No. 2016I2M-1-007, 2018-I2M-1-002) 

主　　题：Stomatin non-small cell lung cancer epithelial-mesenchymal transition TGFβ1 DNA methylation 

摘      要：Objective:Metastasis is one of the key causes of high mortality in lung *** DNA methylation is a common event in metastatic lung *** aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer ***:We screened genes associated with non-small cell lung cancer(NSCLC)metastasis by integrating datasets from the Gene Expression Omnibus(GEO)*** obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation *** overlapping analysis,epigenetically modulated metastasis-associated genes were ***-Meier plotter(KM plotter)was utilized to assess the overall survival(OS)of stomatin in lung ***(IHC)was conducted to determine the association between stomatin and metastasis-associated clinical *** in vitro and in vivo assays were performed to investigate the potential role of stomatin in *** regulation mechanisms of transforming growth factorβ1(TGFβ1)on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot ***:A series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA *** KM plotter analysis showed a positive association between stomatin and the OS of lung *** analysis indicated that the decreased stomatin expression is linked with advanced TNM ***-and gainof-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC ***,TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition(EMT).The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor *** underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA ***:Our results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent met