乙型肝炎病毒x蛋白通过靶向miR-200c诱导DNA异常甲基化  

Hepatitis B Virus x Protein Induces Aberrant DNA Methylation by Targeting miR-200c

作　　者：张媛悦 王淑青 刘岩 刘艳坤[2] 李玉辉[5] 李玉凤[2] ZHANG Yuan-Yue;WANG Shu-Qing;LIU Yan;LIU Yan-Kun;LI Yu-Hui;LI Yu-Feng(Graduate School of North China University of Science and Technology,Tangshan 063200,China;Central Laboratory of Cancer Research Institute of Tangshan People's Hospital,Tangshan 063000,China;North China University of Science and Technology School Clinic,Tangshan 063200,China;School of Life Science,North China University of Science and Technology,Tangshan 063200,China;Department of Neurosurgery,Tangshan People's Hospital,Tangshan,063000,China)

机构地区：[1]华北理工大学研究生院,唐山063200 [2]唐山市人民医院肿瘤防治研究所中心实验室,唐山063000 [3]华北理工大学校医院,唐山063200 [4]华北理工大学生命科学学院,唐山063200 [5]唐山市人民医院神经外科,唐山063000

出　　处：《生物化学与生物物理进展》2020年第10期1080-1089,共10页Progress In Biochemistry and Biophysics

摘　　要：乙型肝炎病毒x(hepatitis B virus x,HBx)蛋白是导致肝癌(hepatocellular Carcinoma,HCC)的重要因素.但HBX在HCC形成过程中表观遗传机制尚有待阐明.本研究发现microRNA-200c(miR-200c)在过表达乙型肝炎病毒的HCC中下调,并且其直接靶向DNA甲基转移酶3A(DNA methyltransferase 3A,DNMT3A).此外,miR-200c和DNMT3A在HB诱发的肝癌组织中呈现负相关.乙型肝炎病毒诱导miR-200c下调,进而引起DNMT3A表达上调,导致细胞中肿瘤相关基因的启动子超甲基化.我们对乙型肝炎病毒诱导的肝癌表观遗传学改变进行了进一步研究,并提出一种基于miRNA的靶向治疗乙型肝炎病毒相关肝癌的潜在方法.The hepatitis B virus x(HBx)protein has been implicated in the pathogenesis of HBV-associated hepatocellular carcinoma(HCC).The mechanisms of HBx involved in epigenetic changes during hepatocarcinogenesis are still obscure.We report here that micro RNA-200 c(miR-200c)was downregulated in HBV-expressing HCC cells and it targeted DNMT3 A directly.In addition,an inverse correlation between miR-200c and DNA methyltransferase 3 A(DNMT3 A)was founded in HBV-induced HCC tissues.HBV-induced downregulation of miR-200c upregulated DNMT3 A expression,and then resulted in promoter hypermethylation of tumor-related genes in HCC.Our data supplied an epigenetic insight into HBV-induced HCC and identified a potential mi RNA-based targeted approach for treating HBV-related HCC.

关 键 词：MIR-200C 肝癌 DNMT3A 乙肝病毒 

分 类 号：Q7[生物学—分子生物学]