The Role of Epigenetic Regulation in Epstein-Barr Virus-Associated Gastric Cancer.
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.
['Nishikawa|Jun|J|', 'Iizasa|Hisashi|H|', 'Yoshiyama|Hironori|H|', 'Nakamura|Munetaka|M|', 'Saito|Mari|M|', 'Sasaki|Sho|S|', 'Shimokuri|Kanami|K|', 'Yanagihara|Masashi|M|', 'Sakai|Kouhei|K|', 'Suehiro|Yutaka|Y|', 'Yamasaki|Takahiro|T|', 'Sakaida|Isao|I|']
D000964:Antimetabolites, Antineoplastic D001374:Azacitidine D050677:Core Binding Factor Alpha 3 Subunit D018899:CpG Islands D019175:DNA Methylation D004279:DNA, Viral D000077209:Decitabine D044127:Epigenesis, Genetic D020031:Epstein-Barr Virus Infections D015972:Gene Expression Regulation, Neoplastic D015967:Gene Expression Regulation, Viral D004854:Herpesvirus 4, Human D006801:Humans D035683:MicroRNAs D012367:RNA, Viral D013274:Stomach Neoplasms D000072160:Tumor Protein p73
epigenetics gastric cancer epstein-barr virus microRNA non-coding RNA demethylating agent DNA methylation