多组学分析揭示Grb2介导α-硫辛酸抑制肝癌细胞增殖研究  

Multi-omics Analyses Reveal α-lipoic acid-regulated Cell Proliferation via Grb2-mediated Signaling Downregulation

作　　者：杨澜[1] 邓兴明[2] 李贝 邓雪松[3] 陆菁潇 吕国庆[2] YANG Lan;DENG Xing-ming;LIBei;DENG Xue-song;LU Jing-xiao;L V Guo-qing(Institute of Translational Medicine,Shenzhen Second People＇s Hospital,Shenzhen,Guangdong,518035,China;Department of Gastrointestinal Surgery,Peking University Shenzhen Hospital,Guangdong,Shenzhen,518036,China;Department of Hepatobiliary Surgery,Shenzhen Second People＇s Hospital,Shenzhen,Guangdong,518035,China)

机构地区：[1]深圳市第二人民医院转化医学研究院,广东深圳518035 [2]北京大学深圳医院胃肠外科,广东深圳518036 [3]深圳市第二人民医院肝胆外科,广东深圳518035

出　　处：《现代生物医学进展》2018年第20期3817-3823,共7页Progress in Modern Biomedicine

基　　金：国家自然科学基金面上项目(81672813);人事部中国博士后科学基金项目(2016M602594);深圳市科技计划2016年基础研究项目(JCYJ20160425105945739);深圳市"三名工程"(SZSM201612051)

摘　　要：目的:为更深入了解α-硫辛酸如何影响复杂信号通路间的相互作用抑制细胞增殖。方法:我们凭借RNA-Seq与同位素相对标记与绝对定量技术,对α-LA处理24 h HepG2细胞在转录和蛋白表达水平的变化差异进行分析,并借助实时定量PCR免疫印迹技术对组学数据进行了鉴定。结果:转录组学提示共有4,446个基因(2,097个基因表达下调,2,349个基因表达上调)的表达在α-LA处理24 h后呈现显著性改变。GO分析提示,编码肿瘤相关细胞膜蛋白的基因是受α-LA影响最为显著的一类mRNA;蛋白质组学进一步提示Grb2可能是受α-LA调控的膜受体信号通路中关键的靶分子。结论:α-LA抑制HCC细胞增殖是通过下调Grb2介导的相关通路而实现。Objective： To more comprehensively understand how a-LA mediates the components of the complex web of interactions among the signalling pathways to repression the cell proliferation. Methods： In this study, we combined the use of an RNA sequencing（RNA-Seq） database and isobaric tag for relative and absolute quantitation（i TRAQ）-based quantitative proteomics data to investigate the dynamic genomic/proteomic response of HepG2 cells to α-LA stress. Real-time PCR and western blotting were used to identified the expression changes of key genes which from the omics. Results： A total of 4,446 differentially expressed genes（2,097 downregulated and 2,349 upregulated） were identified via RNA-Seq in HepG2 cells after exposure to α-LA for 24 h. Moreover, GO analyses showed mRNA that encode cancer-relevant cell membrane proteins were significantly affected. A further proteomic analysis predicted that Grb2 may mediate the key target pathways activated by exposure to α-LA. Conclusion： These findings provide a novel mechanism by which α-LA regulates cell proliferation via the downregulation of growth factor-stimulated Grb2 signaling.

关 键 词：Α-硫辛酸 肝细胞癌 细胞增殖 GRB2 

分 类 号：R-33[医药卫生] R735.7