Role of Viral miRNAs and Epigenetic Modifications in Epstein-Barr Virus-Associated Gastric Carcinogenesis

Table 1

List of main EBV-associated gastric carcinogenesis studies discussed in this review.

First author and year of publication	Study design	Paper number in references section	Summary of findings
Yau et al., 2014	Review	[10]	EBV infection contributes to gastric carcinogenesis through the expression of viral proteins and microRNAs as well as aberrant DNA methylation and histone modification and relative therapeutic implications.
Shinozaki-Ushiku et al., 2015	Review	[57]	In the present review latest findings on EBVaGC from clinicopathological and molecular perspectives were discussed to provide a better understanding of EBV involvement in gastric carcinogenesis. In addition to genetic and epigenetic changes, posttranscriptional gene expression regulation by cellular and/or EBV-derived microRNAs was also considered.
Shinozaki-Ushiku et al., 2015	Experimental; research	[90]	Comprehensive profile of the expression of 44 known EBV miRNAs from EBV-associated gastric carcinoma patients was presented. Of several highly expressed EBV miRNAs, EBV-miR-BART4-5p plays a partial role in suppressing proapoptotic protein Bid, leading to reduced apoptosis. The present work provides novel insights into the roles played by EBV miRNAs in gastric carcinogenesis and identifies future potential therapeutic targets.
Kim et al., 2015	Experimental; research	[91]	miR-BART20-5p contributes to the tumorigenesis initiation and/or maintenance of EBVaGC by directly targeting 3′-UTR of Bcl-2-associated death promoter (BAD) involved in cell proliferation and apoptosis. Inhibition of miR-BART20-5p can exert a therapeutic effect for this neoplasia.
Kanda et al., 2015	Experimental; research	[92]	A causative relationship between BART miRNA expression and epithelial carcinogenesis in vivo was demonstrated. In particular, it was shown that NDRG1 protein, which is a putative target of BART miRNAs, can be used as an epithelial differentiation marker and a suppressor of metastasis.
Fu et al., 2013	Review	[94]	Potential mechanisms by which EBV contributes to its own latency and the formation tumors including EBVaGC were considered. Particularly, this review describes the interactions of EBV gene products including viral miRNAs and the Bcl-2 family members involved in cell death (apoptosis) and survival pathways. A better understanding of this complicated network of interactions could be of great importance for creating novel therapeutic strategies for EBV-associated diseases.
Tokunaga et al., 1993	Epidemiological; research	[104]	EBV infection contributed significantly to gastric carcinogenesis in Japan. It occurred predominantly in males, especially in cancers of the upper and middle parts of the stomach, with greater cell type variation in men, suggesting that novel factors may play important causal roles in EBV-associated gastric carcinogenesis.