The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas

Epstein-Barr virus (EBV) is an important DNA virus which establishes latent infection in human malignancies. Expression of EBV-encoded genes in the associated tumors is strongly modulated by promoter CpG methylation of EBV genome. This study aimed to explore the methylation status of the promoters o...

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Main Authors: Jing Li, Wen Liu, Kui Che, Yan Zhang, Zhenzhen Zhao, Bing Luo
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2017/3804146
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author Jing Li
Wen Liu
Kui Che
Yan Zhang
Zhenzhen Zhao
Bing Luo
author_facet Jing Li
Wen Liu
Kui Che
Yan Zhang
Zhenzhen Zhao
Bing Luo
author_sort Jing Li
collection DOAJ
description Epstein-Barr virus (EBV) is an important DNA virus which establishes latent infection in human malignancies. Expression of EBV-encoded genes in the associated tumors is strongly modulated by promoter CpG methylation of EBV genome. This study aimed to explore the methylation status of the promoters of EBV BamHI-A rightward frame 1 (BARF1) and BamHI-H rightward open reading frame 1 (BHRF1) and their influence on transcriptional expression, to further understand the roles of BARF1 and BHRF1 in the occurrence of EBV-associated cancer. We evaluated the methylation status of BARF1 and BHRF1 promoters in 43 EBV-associated gastric carcinoma (EBVaGC) tissues and EBV-positive cell lines. Their expressions were evaluated by real-time quantitative PCR. We found that the promoters of BARF1 and BHRF1 were methylated by varying degrees in different EBV-positive cell lines and were almost hypermethylated in all EBVaGC tissues. The methylation status of BARF1 and BHRF1 promoters were significantly reduced by 5-Aza-CdR along with the increasing gene expressions. Hypermethylation of Ap and Hp mediates the frequent silencing of BARF1 and BHRF1 in EBV-associated tumors, which could be reactivated by a demethylation agent, suggesting that promoter demethylation and activation is important for BARF1 and BHRF1 transcription and their further action.
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spelling doaj-art-422c81cf5f37404d82d2e52ce4e14f592025-08-20T03:55:43ZengWileyGastroenterology Research and Practice1687-61211687-630X2017-01-01201710.1155/2017/38041463804146The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric CarcinomasJing Li0Wen Liu1Kui Che2Yan Zhang3Zhenzhen Zhao4Bing Luo5Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, 19 Jiangsu Road, Qingdao 266003, ChinaDepartment of Medical Microbiology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, ChinaDepartment of Central Laboratory, The Affiliated Hospital of Qingdao University, 19 Jiangsu Road, Qingdao 266003, ChinaDepartment of Medical Microbiology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, ChinaDepartment of Medical Microbiology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, ChinaDepartment of Medical Microbiology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, ChinaEpstein-Barr virus (EBV) is an important DNA virus which establishes latent infection in human malignancies. Expression of EBV-encoded genes in the associated tumors is strongly modulated by promoter CpG methylation of EBV genome. This study aimed to explore the methylation status of the promoters of EBV BamHI-A rightward frame 1 (BARF1) and BamHI-H rightward open reading frame 1 (BHRF1) and their influence on transcriptional expression, to further understand the roles of BARF1 and BHRF1 in the occurrence of EBV-associated cancer. We evaluated the methylation status of BARF1 and BHRF1 promoters in 43 EBV-associated gastric carcinoma (EBVaGC) tissues and EBV-positive cell lines. Their expressions were evaluated by real-time quantitative PCR. We found that the promoters of BARF1 and BHRF1 were methylated by varying degrees in different EBV-positive cell lines and were almost hypermethylated in all EBVaGC tissues. The methylation status of BARF1 and BHRF1 promoters were significantly reduced by 5-Aza-CdR along with the increasing gene expressions. Hypermethylation of Ap and Hp mediates the frequent silencing of BARF1 and BHRF1 in EBV-associated tumors, which could be reactivated by a demethylation agent, suggesting that promoter demethylation and activation is important for BARF1 and BHRF1 transcription and their further action.http://dx.doi.org/10.1155/2017/3804146
spellingShingle Jing Li
Wen Liu
Kui Che
Yan Zhang
Zhenzhen Zhao
Bing Luo
The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas
Gastroenterology Research and Practice
title The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas
title_full The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas
title_fullStr The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas
title_full_unstemmed The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas
title_short The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas
title_sort methylation status and expression of epstein barr virus early genes barf1 and bhrf1 in epstein barr virus associated gastric carcinomas
url http://dx.doi.org/10.1155/2017/3804146
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