Nishikawa Jun, Iizasa Hisashi, Yoshiyama Hironori, Nakamura Munetaka, Saito Mari, Sasaki Sho, Shimokuri Kanami, Yanagihara Masashi, Sakai Kouhei, Suehiro Yutaka, Yamasaki Takahiro, Sakaida Isao
Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Department of Microbiology, Shimane University Faculty of Medicine, 89-1 Enyacho, Izumo City, Shimane 693-8501, Japan.
Int J Mol Sci. 2017 Jul 25;18(8):1606. doi: 10.3390/ijms18081606.
The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma (EBVaGC), all tumor cells harbor the clonal EBV genome. The expression of latent EBV genes is strictly regulated through the methylation of EBV DNA. The methylation of viral DNA regulates the type of EBV latency, and methylation of the tumor suppressor genes is a key abnormality in EBVaGC. The methylation frequencies of several tumor suppressor genes and cell adhesion molecules are significantly higher in EBVaGC than in control cases. EBV-derived microRNAs repress translation from viral and host mRNAs. EBV regulates the expression of non-coding RNA in gastric carcinoma. With regard to the clinical application of demethylating agents against EBVaGC, we investigated the effects of decitabine against the EBVaGC cell lines. Decitabine inhibited the cell growth of EBVaGC cells. The promoter regions of p73 and Runt-related transcription factor 3(RUNX3) were demethylated, and their expression was upregulated by the treatment. We review the role of epigenetic regulation in the development and maintenance of EBVaGC and discuss the therapeutic application of DNA demethylating agents for EBVaGC.
在全球约10%的胃癌病例中可检测到爱泼斯坦-巴尔病毒（EBV）。在EBV相关胃癌（EBVaGC）中，所有肿瘤细胞都含有克隆性EBV基因组。EBV潜伏基因的表达通过EBV DNA的甲基化受到严格调控。病毒DNA的甲基化调节EBV潜伏类型，肿瘤抑制基因的甲基化是EBVaGC的关键异常。与对照病例相比，EBVaGC中几种肿瘤抑制基因和细胞粘附分子的甲基化频率显著更高。EBV衍生的微小RNA抑制病毒和宿主mRNA的翻译。EBV调节胃癌中非编码RNA的表达。关于去甲基化剂对EBVaGC的临床应用，我们研究了地西他滨对EBVaGC细胞系的影响。地西他滨抑制了EBVaGC细胞的生长。p73和Runt相关转录因子3（RUNX3）的启动子区域去甲基化，并且它们的表达通过该处理而上调。我们综述了表观遗传调控在EBVaGC发生和维持中的作用，并讨论了DNA去甲基化剂在EBVaGC治疗中的应用。
