Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells.
Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells.
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Epstein-Barr 病毒在恶性上皮细胞中诱导细胞高 CpG 甲基化的致癌作用。
DOI：
10.5732/cjc.014.10191
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发表时间：
2014-12
影响因子：
--
通讯作者：
Tao Q
中科院分区：
文献类型：
--
作者：
Li L;Zhang Y;Guo BB;Chan FK;Tao Q
EB病毒是一种著名的人类疱疹病毒，与全世界几乎所有的鼻咽癌和∼10%的胃癌有关。越来越多的证据表明，获得性遗传和表观遗传改变导致鼻咽癌和胃癌的发生和发展。然而，即使是深层的外显子测序研究也显示，鼻咽癌和EBV相关胃癌(EBVaGC)中基因突变的频率相对较低，这表明表观遗传学异常，特别是启动子CpG甲基化在鼻咽癌和EBVaGC的发病机制中起主导作用。在鼻咽癌和EBVaGC中，肿瘤抑制基因(TSG)启动子甲基化的频率很高，并发现了几种EBV诱导的TSG甲基化。对鼻咽癌和EBVaGC的表观基因组(全基因组CpG甲基化图谱-甲基组)的进一步分析表明，这些EBV相关肿瘤表现出独特的高CpG甲基化表型和更广泛的基因甲基化积累，表明EBV是这些癌症的直接表观遗传学驱动因素。从机制上讲，EBV编码的病毒蛋白对细胞内CpG甲基化机制(如DNA甲基转移酶(DNMT))的致癌调控是EBV诱导的鼻咽癌和EBVaGC中高CpG甲基化表型的原因。因此，揭示EBV相关的鼻咽癌和EBVaGC的独特表观类型将为了解这些独特的EBV相关肿瘤的分子发病机制提供新的见解，并进一步有助于开发针对这些恶性肿瘤细胞甲基化机制的药物治疗策略。
Epstein-Barr virus (EBV) is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma (NPC) and ∼10% of gastric cancer (GC) worldwide. Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC. However, even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC (EBVaGC), suggesting a predominant role of epigenetic abnormities, especially promoter CpG methylation, in the pathogenesis of NPC and EBVaGC. High frequencies of promoter methylation of tumor suppressor genes (TSGs) have been frequently reported in NPC and EBVaGC, with several EBV-induced methylated TSGs identified. Further characterization of the epigenomes (genome-wide CpG methylation profile—methylome) of NPC and EBVaGC shows that these EBV-associated tumors display a unique high CpG methylation epigenotype with more extensive gene methylation accumulation, indicating that EBV acts as a direct epigenetic driver for these cancers. Mechanistically, oncogenic modulation of cellular CpG methylation machinery, such as DNA methyltransferases (DNMTs), by EBV-encoded viral proteins accounts for the EBV-induced high CpG methylation epigenotype in NPC and EBVaGC. Thus, uncovering the EBV-associated unique epigenotype of NPC and EBVaGC would provide new insight into the molecular pathogenesis of these unique EBV-associated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.
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影响因子：
6.7
作者：
Kong QL;Hu LJ;Cao JY;Huang YJ;Xu LH;Liang Y;Xiong D;Guan S;Guo BH;Mai HQ;Chen QY;Zhang X;Li MZ;Shao JY;Qian CN;Xia YF;Song LB;Zeng YX;Zeng MS
通讯作者：
Zeng MS
DOI：
10.1073/pnas.0700153104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Jin, Hongchuan;Wang, Xian;Tao, Qian
通讯作者：
Tao, Qian
影响因子：
11.2
作者：
Cheng, Yingduan;Geng, Hua;Tao, Qian
通讯作者：
Tao, Qian
影响因子：
4.8
作者：
Kanda, Teru;Horikoshi, Naoki;Tsurumi, Tatsuya
通讯作者：
Tsurumi, Tatsuya
影响因子：
30.8
作者：
Lin, De-Chen;Meng, Xuan;Koeffler, H. Phillip
通讯作者：
Koeffler, H. Phillip