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Methylation and expression of Epstein-Barr virus latent membrane protein 1, 2A and 2B in EBV-associated gastric carcinomas and cell lines.
Methylation and expression of Epstein-Barr virus latent membrane protein 1, 2A and 2B in EBV-associated gastric carcinomas and cell lines.
- Source :
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Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver [Dig Liver Dis] 2016 Jun; Vol. 48 (6), pp. 673-80. Date of Electronic Publication: 2016 Mar 02. - Publication Year :
- 2016
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Abstract
- Background: Promoter CpG methylation of Epstein-Barr virus (EBV) genome plays an essential role in maintaining viral latency. Latent membrane protein (LMP) 1, 2A and 2B of EBV exert multiple oncogenic properties by activating multiple signal pathways and modulating the expression of various oncogenes.<br />Aims: To study the methylation and expression of LMP1, 2A and LMP2B in EBV-positive cell lines and EBV-associated tumors.<br />Methods: The methylation profiles of LMP1p, LMP2Ap and LMP2Bp were evaluated by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP), as well as their expression by quantitative real-time (qRT)-PCR in 41 EBV-associated carcinomas (EBVaGCs) and 5 EBV-positive cell lines.<br />Results: All LMP promoters were methylated at different degrees in EBV-positive cell lines and hypermethylated in EBV-associated gastric carcinomas, while unmethylated LMP2Ap alleles were detected in B95-8 cell line. Following 5-aza-2'-deoxycytidine (5-aza) treatment, the LMP1 expression was restored along with concomitant promoter demethylation; changes of LMP2A and LMP2B expression were different in different cells.<br />Conclusion: Methylation of LMP1, 2A and 2B promoters mediates the silencing of LMP1, 2A and 2B in EBV-associated carcinomas and cell lines in varying degrees, and could be reactivated by demethylation agent and thus may contribute to the therapy of EBVaGCs.<br /> (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Azacitidine analogs & derivatives
Azacitidine pharmacology
Cell Line, Tumor
Decitabine
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Promoter Regions, Genetic
Stomach Neoplasms virology
DNA Methylation
Epstein-Barr Virus Infections complications
Herpesvirus 4, Human physiology
Stomach Neoplasms genetics
Viral Matrix Proteins genetics
Virus Latency
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3562
- Volume :
- 48
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 27026080
- Full Text :
- https://doi.org/10.1016/j.dld.2016.02.017