EBV-associated Histone Modifications in the Regulation of DNA Damage Repair Members in Nasopharyngeal Carcinoma.

Abstract

Infection of an oncovirus, Epstein - Barr virus (EBV), is associated with certain cancers including nasopharygeal carcinoma (NPC). However, the possible roles of EBV in NPC development are still poorly understood. In this study, we aimed to elucidate the roles of EBV in the regulation of DNA damage repair members via histone modifications H3K4me3. Two pairs of EBV-positive and EBV-negative nasopharygeal epithelial (NPE) cell lines were used for chromatin immunoprecipitation sequencing (ChIP-Seq) to identify EBV-regulated genes in the host cells. Totally, 18 DNA damage repair signalling members showed significant losses of H3K4me3 in EBV-infected NPE cells. Among all the candidate genes, 7 base excision repair (BER) members, APEX, POLB , POLD1 , PCNA, TDG, OGG1, and NEIL3 , and a mismatch repair (MMR) member, MLH1 , showed significant downregulation in the EBV-infected cells. The clinical significance was further confirmed by detection of significant down-regulation of the BER members and MLH1 in NPC paired biopsies. Our results suggested EBV infection induces loss of H3K4me3 in the BER members and MLH1 , resulting in downregulation in the EBV-infected cells and NPC tumor biopsies.