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Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells

Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcin...

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Autores principales: Pandey, Saurabh, Jha, Hem Chandra, Shukla, Sanket Kumar, Shirley, Meghan K., Robertson, Erle S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915740/
https://www.ncbi.nlm.nih.gov/pubmed/29691341
http://dx.doi.org/10.1128/mBio.00649-18
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author Pandey, Saurabh
Jha, Hem Chandra
Shukla, Sanket Kumar
Shirley, Meghan K.
Robertson, Erle S.
author_facet Pandey, Saurabh
Jha, Hem Chandra
Shukla, Sanket Kumar
Shirley, Meghan K.
Robertson, Erle S.
author_sort Pandey, Saurabh
collection PubMed
description Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further, H. pylori-EBV coinfection causes chronic inflammation in pediatric patients. We have established an H. pylori-EBV coinfection model system using human gastric epithelial cells. We showed that H. pylori infection can increase the oncogenic phenotype of EBV-infected cells and that the cytotoxin-associated gene (CagA) protein encoded by H. pylori stimulated EBV-mediated cell proliferation in this coinfection model system. This led to increased expression of DNA methyl transferases (DNMTs), which reprogrammed cellular transcriptional profiles, including those of tumor suppressor genes (TSGs), through hypermethylation. These findings provide new insights into a molecular mechanism whereby cooperativity between two oncogenic agents leads to enhanced oncogenic activity of gastric cancer cells.
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spelling pubmed-59157402018-05-01 Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells Pandey, Saurabh Jha, Hem Chandra Shukla, Sanket Kumar Shirley, Meghan K. Robertson, Erle S. mBio Research Article Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further, H. pylori-EBV coinfection causes chronic inflammation in pediatric patients. We have established an H. pylori-EBV coinfection model system using human gastric epithelial cells. We showed that H. pylori infection can increase the oncogenic phenotype of EBV-infected cells and that the cytotoxin-associated gene (CagA) protein encoded by H. pylori stimulated EBV-mediated cell proliferation in this coinfection model system. This led to increased expression of DNA methyl transferases (DNMTs), which reprogrammed cellular transcriptional profiles, including those of tumor suppressor genes (TSGs), through hypermethylation. These findings provide new insights into a molecular mechanism whereby cooperativity between two oncogenic agents leads to enhanced oncogenic activity of gastric cancer cells. American Society for Microbiology 2018-04-24 /pmc/articles/PMC5915740/ /pubmed/29691341 http://dx.doi.org/10.1128/mBio.00649-18 Text en Copyright © 2018 Pandey et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Pandey, Saurabh
Jha, Hem Chandra
Shukla, Sanket Kumar
Shirley, Meghan K.
Robertson, Erle S.
Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells
title Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells
title_full Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells
title_fullStr Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells
title_full_unstemmed Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells
title_short Epigenetic Regulation of Tumor Suppressors by Helicobacter pylori Enhances EBV-Induced Proliferation of Gastric Epithelial Cells
title_sort epigenetic regulation of tumor suppressors by helicobacter pylori enhances ebv-induced proliferation of gastric epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915740/
https://www.ncbi.nlm.nih.gov/pubmed/29691341
http://dx.doi.org/10.1128/mBio.00649-18
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