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

Yingxue Gao; Yuxin Fu; Jia Wang; Xiang Zheng; Jianhua Zhou; Jian Ma

doi:10.1016/j.bbrc.2021.02.014

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

Biochem Biophys Res Commun. 2021 Apr 2:547:1-8. doi: 10.1016/j.bbrc.2021.02.014. Epub 2021 Feb 12.

Authors

Yingxue Gao¹, Yuxin Fu¹, Jia Wang², Xiang Zheng², Jianhua Zhou³, Jian Ma⁴

Affiliations

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: zhoujh15@163.com.
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: majian@csu.edu.cn.

PMID: 33588233
DOI: 10.1016/j.bbrc.2021.02.014

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.

Keywords: DNA methylation; Epstein-Barr virus; Gastric cancer; LMP1; RASSF10.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation / physiology
DNA (Cytosine-5-)-Methyltransferase 1 / genetics
DNA (Cytosine-5-)-Methyltransferase 1 / metabolism*
DNA Methylation*
Epigenesis, Genetic
Epstein-Barr Virus Infections / metabolism*
Epstein-Barr Virus Infections / pathology
Epstein-Barr Virus Infections / virology
Female
Herpesvirus 4, Human / isolation & purification
Humans
Male
Mice
Mice, Nude
Middle Aged
Neoplasm Staging
Risk Factors
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology*
Stomach Neoplasms / virology*
Tumor Suppressor Proteins / antagonists & inhibitors
Tumor Suppressor Proteins / genetics*
Tumor Suppressor Proteins / metabolism
Viral Matrix Proteins / genetics
Viral Matrix Proteins / metabolism*

Substances

EBV-associated membrane antigen, Epstein-Barr virus
RASSF10 protein, human
Tumor Suppressor Proteins
Viral Matrix Proteins
DNA (Cytosine-5-)-Methyltransferase 1
DNMT1 protein, human