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标题：Downregulation of HLA-ABC expression through promoter hypermethylation and downmodulation of MIC-A/B surface expression in LMP2A-positive epithelial carcinoma cell lines
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作者：Shweta Singh ; Subrata Banerjee
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-12
DOI：10.1038/s41598-020-62081-0
出版社：Springer Nature
摘要：Epstein Barr Virus (EBV) is a human herpesvirus, and has been reported to be associated with nasopharyngeal carcinoma, gastric carcinoma, Burkitt’s lymphoma and Hodgkin’s lymphoma. In most of the associated tumors, the virus remains in a latently infected state. During latency, EBV expresses Latent Membrane Protein 2A (LMP2A) along with few other genes. We previously showed that LMP2A causes downregulation of HLA-ABC surface expression in EBV associated gastric carcinomas. However, the mechanism that leads to this downregulation remain unclear. We therefore analyzed methylation-mediated regulation of HLA-ABC expression by LMP2A. Interestingly, according to the ‘missing self’ hypothesis, when there is a decrease in HLA-ABC surface expression, expression of NKG2D ligands’ must be upregulated to facilitate killing by Natural Killer (NK) cells. Analysis of NKG2D ligands’ expression, revealed downregulation of MIC-A/B surface expression in response to LMP2A. Furthermore, the role of Unfolded Protein Response (UPR) in the regulation of MIC-A/B surface expression in cells expressing LMP2A was also investigated. Protein Disulfide Isomerase (PDI) mediated inhibition of MIC-A/B surface expression was observed in LMP2A expressing cells. Our current findings provide new insights in LMP2A arbitrated dysregulation of host immune response in epithelial cell carcinomas.