甲基化CpG结合蛋白2的泛癌分析及其对肝癌Hep3B细胞生物活性的影响  

Pan-cancer analysis of MeCP2 and its effect on the biological activity of liver carcinoma Hep3B cells

作　　者：杨阳 孙瑞芳[2] 李玉龙[3] 孙娜 YANG Yang;SUN Ruifang;LI Yulong;SUN Na(Department of Hygiene Toxicology,School of Public Health,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Department of Pathology,School of Basic Medical Sciences,Xi’an Jiaotong University;Department of Gastroenterology,Shaanxi Provincial People’s Hospital)

机构地区：[1]陕西中医药大学公共卫生学院卫生毒理学教研室,咸阳712046 [2]西安交通大学基础医学院病理学系 [3]陕西省人民医院消化内科

出　　处：《山西医科大学学报》2022年第9期1047-1052,共6页Journal of Shanxi Medical University

基　　金：陕西中医药大学校内科研基金资助项目(2021GP18,17102032234)。

摘　　要：目的应用生物信息学方法分析甲基化CpG结合蛋白2(methyl-CpG-binding domain protein 2,MeCP2)在多种肿瘤中的作用并在肝癌细胞中对其进行验证。方法利用肿瘤免疫评估资源(Tumor Immune Estimation Resource 2.0,TIMER 2.0)、基因表达谱交互分析(Gene Expression Profiling Interactive Analysis 2,GEPIA 2)和癌症基因组学门户网站(cBioPortal for Cancer Genomics,cBioPortal)分析MeCP2基因在多种肿瘤组织中的表达,MeCP2对肿瘤患者生存期的影响及其在肿瘤中遗传变异的情况。应用CCK-8及细胞周期实验分别检测过表达和沉默MeCP2对肝癌Hep3B细胞增殖及细胞周期的影响。结果TIMER2.0显示,与正常组织相比,MeCP2在乳腺浸润癌、胆管癌、食管癌、头颈鳞状细胞癌、肾嫌色细胞癌、肝细胞癌中的mRNA表达水平显著增加(P<0.05);GEPIA2结果显示MeCP2与乳腺浸润癌、结肠癌、肾乳头状细胞癌、肝细胞癌、肾透明细胞癌、葡萄膜黑色素瘤的预后相关。cBioPortal分析提示错义突变是MeCP2基因突变的主要类型。CCK-8实验表明过表达MeCP2可促进肝癌Hep3B细胞增殖(P<0.05),而抑制其表达可抑制肝癌Hep3B细胞增殖(P<0.01);细胞周期实验表明抑制MeCP2可将肝癌Hep3B细胞阻滞在G1期(P<0.01)。结论MeCP2在肝癌中可能发挥癌基因的作用。Objective To analyze the function of methyl-CpG-binding domain protein 2(MeCP2)in tumors by bioinformatics analysis and validate the effect of MeCP2 on liver cancer cells.Methods Tumor Immune Estimation Resource 2.0(TIMER2.0),Gene Expression Profiling Interactive Analysis 2(GEPIA2)and cBioPortal for Cancer Genomics(cBioPortal)were used to analyze the expression of MeCP2 gene in various tumor tissues and the effect of MeCP2 expression on the survival of tumor patients and the mutation of MeCP2.The effects of overexpression and silencing of MeCP2 on the proliferation and the cell cycle of liver cancer Hep3B cells were detected by CCK-8 and cell cycle assays.Results TIMER2.0 showed that the mRNA expression levels of MeCP2 in breast invasive carcinoma,cholangiocarcinoma,esophageal carcinoma,head and neck squamous cell carcinoma,kidney chromophobe,and liver hepatocellular carcinoma were significantly increased compared with normal tissues(P<0.05).GEPIA2 showed that MeCP2 was associated with the prognosis of breast invasive carcinoma,colon adenocarcinoma,kidney renal papillary cell carcinoma,liver hepatocellular carcinoma,kidney renal clear cell carcinoma,uveal melanoma.cBioPortal analysis suggested that the missense mutations were the main type of MeCP2 gene mutations.CCK-8 experiments showed that the overexpression of MeCP2 promoted the proliferation of liver cancer Hep3B cells(P<0.05),and the inhibition of MeCP2 expression inhibited the proliferation of Hep3B cells(P<0.01).Cell cycle experiments showed that the inhibition of MeCP2 caused Hep3B cells to arrest in G1 phase(P<0.01).Conclusion The above results suggest that MeCP2 may play an oncogene role in liver carcinoma.

关 键 词：MECP2 生物信息学 肝癌 增殖 

分 类 号：R735.7[医药卫生—肿瘤]