Abstract
The Epstein–Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma (EBVaGC), all tumor cells harbor the clonal EBV genome. The expression of latent EBV genes is strictly regulated through the methylation of EBV DNA. The methylation of viral DNA regulates the type of EBV latency, and methylation of the tumor suppressor genes is a key abnormality in EBVaGC. The methylation frequencies of several tumor suppressor genes and cell adhesion molecules are significantly higher in EBVaGC than in control cases. EBV-derived microRNAs repress translation from viral and host mRNAs. EBV regulates the expression of non-coding RNA in gastric carcinoma. With regard to the clinical application of demethylating agents against EBVaGC, we investigated the effects of decitabine against the EBVaGC cell lines. Decitabine inhibited the cell growth of EBVaGC cells. The promoter regions of p73 and Runt-related transcription factor 3(RUNX3) were demethylated, and their expression was upregulated by the treatment. We review the role of epigenetic regulation in the development and maintenance of EBVaGC and discuss the therapeutic application of DNA demethylating agents for EBVaGC.
Highlights
Gastric cancer is the third leading cause of cancer-related mortality and is responsible for approximately 450,000 deaths worldwide each year [1,2]
Marquitz et al reported that Bam HI-A transcripts (BARTs) Long Non-Coding RNA (lncRNA) reduced the expression of amino acid transporter xCT, cadherin superfamily CDH11, and E3 ubiquitin ligase RNF144B [66]. xCT is a glutamate-cystine transporter that is highly expressed in cancer stem cells to erase reactive oxygen species [67]
We examined the effect of another demethylating agent, zebularine, and found that it inhibited the growth of SNU719 and NCC24 cells, which were derived from Epstein–Barr virus (EBV)-positive gastric adenocarcinoma [81]
Summary
Gastric cancer is the third leading cause of cancer-related mortality and is responsible for approximately 450,000 deaths worldwide each year [1,2]. EBNA promoters (Cp and Wp), which can transcribe all EBNAs, are hypermethylated in tumors showing type I latency, and the alternative EBNA promoter Qp is used [21,22] These results indicate that the methylation status of the EBV genome regulates the pattern of latent gene expression in EBV-positive tumor cells. A systemic review by Ribeiro et al showed that the most frequently expressed EBV latent proteins are EBNA1 (98.1%) and LMP2A (53.8%), whereas LMP1 and LMP2B are present in only 10% of cases. Lytic proteins, such as BARF0 and BARF1, and other lytic transcripts are present in almost half of the cases [27]. The methylation of viral DNA determines the type of EBV latency, which may contribute to the maintenance of EBVaGC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
