EBV as a high infection risk factor promotes RASSF10 methylation and induces cell proliferation in EBV-associated gastric cancer.

Affiliation

Gao Y(1), Fu Y(1), Wang J(2), Zheng X(2), Zhou J(3), Ma J(4).
Author information:
(1)Xiangya Hospital, Department of Pathology, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 410008, China.
(2)Xiangya Hospital, Department of Pathology, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, NHC Key Laboratory of Carcinogenesis, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Changsha, Hunan, China.
(3)Xiangya Hospital, Department of Pathology, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 410008, China. Electronic address: [Email]
(4)Xiangya Hospital, Department of Pathology, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, NHC Key Laboratory of Carcinogenesis, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Changsha, Hunan, China. Electronic address: [Email]

Abstract

Epstein-Barr virus (EBV) is the first identified human tumor-related DNA virus, and has a high infection among people worldwide. Recent studies have showed that nearly 10% of gastric cancers have shown EBV infection and this kind of gastric cancer has been identified as a new subtype: EBV associated Gastric cancer (EBVaGC). Furthermore, it has been reported that tumor related genes in the EBVaGC showed frequent methylation modifications compared to those in the EBV negative gastric cancer (EBVnGC). To fully understand the role of EBV in EBVaGC, we analyzed and found that 16.67% of gastric carcinoma samples showed positive EBER1 signals. Mechanically, EBV-encoded Latent membrane protein 1 (LMP1) inhibited the expression of RASSF10, and promoted tumorigenesis by recruiting DNMT1 and inducing the DNA methylation of RASSF10. Altogether, it allows us a better understanding of the possible mechanism of EBV-induced gene hypermethylation in gastric cancer genome. Targeting EBV-induced DNA methylation is a potential therapeutic modality of EBVaGC.