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Int. J. Mol. Sci. 2017, 18(8), 1606; doi:10.3390/ijms18081606

The Role of Epigenetic Regulation in Epstein-Barr Virus-Associated Gastric Cancer

1
Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
2
Department of Microbiology, Shimane University Faculty of Medicine, 89-1 Enyacho, Izumo City, Shimane 693-8501, Japan
3
Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
4
Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
*
Author to whom correspondence should be addressed.
Received: 6 July 2017 / Revised: 19 July 2017 / Accepted: 22 July 2017 / Published: 25 July 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2743 KB, uploaded 25 July 2017]   |  

Abstract

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. View Full-Text
Keywords: epigenetics; epstein-barr virus; gastric cancer; DNA methylation; microRNA; non-coding RNA; demethylating agent epigenetics; epstein-barr virus; gastric cancer; DNA methylation; microRNA; non-coding RNA; demethylating agent
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Nishikawa, J.; Iizasa, H.; Yoshiyama, H.; Nakamura, M.; Saito, M.; Sasaki, S.; Shimokuri, K.; Yanagihara, M.; Sakai, K.; Suehiro, Y.; Yamasaki, T.; Sakaida, I. The Role of Epigenetic Regulation in Epstein-Barr Virus-Associated Gastric Cancer. Int. J. Mol. Sci. 2017, 18, 1606.

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