EBV infection alters DNA methylation in primary human colon cells: A path to inflammation and carcinogenesis?

Autor: Santarelli R; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy. Electronic address: roberta.santarelli@uniroma1.it., Pascucci GR; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy., Presti SL; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy., Di Crosta M; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy., Benedetti R; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy., Neri A; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy., Gonnella R; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy., Cirone M; Department of Experimental Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy. Electronic address: mara.cirone@uniroma1.it.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Gene regulatory mechanisms [Biochim Biophys Acta Gene Regul Mech] 2024 Dec; Vol. 1867 (4), pp. 195064. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1016/j.bbagrm.2024.195064
Abstrakt: Epstein-Barr Virus (EBV) is associated with several types of human cancers, and changes in DNA methylation are reported to contribute to viral-driven carcinogenesis, particularly in cancers of epithelial origin. In a previous study, we demonstrated that EBV infects human primary colonic cells (HCoEpC) and replicates within these cells, leading to pro-inflammatory and pro-tumorigenic effects. Notably, these effects were mostly prevented by inhibiting viral replication with PAA. Interestingly, the EBV-induced effects correlated with the upregulation of DNMT1 and were counteracted by pretreating cells with 5-AZA, suggesting a role for DNA hypermethylation. Building on this background, the current study investigates the methylation changes induced by EBV infection in HCoEpC, both in the presence and absence of PAA, or ERK1/2 and STAT3 inhibitors, pathways known to be activated by EBV and involved in the dysregulation of methylation in tumor cells. The genome-wide methylation analysis conducted in this study allowed us to identify several biological processes and genes affected by these epigenetic changes, providing insights into the possible underlying mechanisms leading to the pathological effects induced by EBV. Specifically, we found that the virus induced significant methylation changes, with hypermethylation being more prevalent than hypomethylation. Several genes involved in embryogenesis, carcinogenesis, and inflammation were affected.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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