机构：[1]Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China[2]State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China[3]Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China大德路总院珠海院区病理科病理科大德路总院病理科广东省中医院
The hepatitis B virus x protein (HBx) has been implicated as a potential trigger of the epigenetic deregulation of some genes, but the underlying mechanism remains unknown. The aim of this study is to identify underlying mechanisms involved in HBx-mediated epigenetic modification in the process of HBx induced p16(INK4A) promoter hypermethylation. Liver cell lines were stably transfected with HBx-expressing vector. The methylation status of p16(INK4A) was examined by methyl-specific polymerase chain reaction (MSP) and bisulfite sequencing. Reverse transcription and real-time polymerase chain reaction (real-time RT-PCR), Western blot and immunohistochemistry were used to analyze the expression of HBx, HBx-mediated DNA methylation abnormalities and p16(INK4A). Some cases of HCC and corresponding noncancerous liver tissues were studied. HBx up-regulates DNMT1 and DNMT3A expression in both mRNA level and protein level, and HBx represses p16(INK4A) expression through inducing hypermethylation of p16(INK4A) promoter. Moreover. HBx induces hypermethylation of p16(INK4A) promoter through DNMT1 and DNMT3A. Regulation of DNMT1 and DNMT3A by HBx promoted hypermethylation of p16(INK4A) promoter region. HBx-DNMTs-p16(INK4A) promoter hypermethylation may suggest a mechanism for tumorigenesis during hepatocarcinogenesis. (C) 2010 Elsevier Inc. All rights reserved.
基金：
National Natural Science Foundation of China [30770969]; Doctoral Point Fund of University [20070246058]
第一作者机构：[1]Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China[3]Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
通讯作者：
通讯机构：[1]Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China[*1]Department of Pathology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China
推荐引用方式(GB/T 7714)：
Zhu Ya-Zhen,Zhu Rong,Shi Lian-Guo,et al.Hepatitis B virus X protein promotes hypermethylation of p16INK4A promoter through upregulation of DNA methyltransferases in hepatocarcinogenesis[J].EXPERIMENTAL AND MOLECULAR PATHOLOGY.2010,89(3):268-275.doi:10.1016/j.yexmp.2010.06.013.
APA：
Zhu, Ya-Zhen,Zhu, Rong,Shi, Lian-Guo,Mao, Yi,Zheng, Guang-Juan...&Zhu, Hong-Guang.(2010).Hepatitis B virus X protein promotes hypermethylation of p16INK4A promoter through upregulation of DNA methyltransferases in hepatocarcinogenesis.EXPERIMENTAL AND MOLECULAR PATHOLOGY,89,(3)
MLA：
Zhu, Ya-Zhen,et al."Hepatitis B virus X protein promotes hypermethylation of p16INK4A promoter through upregulation of DNA methyltransferases in hepatocarcinogenesis".EXPERIMENTAL AND MOLECULAR PATHOLOGY 89..3(2010):268-275
