Critical review of Epstein–Barr virus microRNAs relation with EBV‐associated gastric cancer

Abstract Epstein–Barr virus (EBV)‐associated gastric cancer (EBVaGC) is regarded as the most prevalent malignant tumor triggered by EBV infection. In recent years, increasing attention has been considered to recognize more about the disease process's exact mechanisms. There is accumulating evidence that showing epigenetic modifications play critical roles in the EBVaGC pathogenesis. MicroRNAs (miRNAs), as critical epigenetic modulators, are single‐strand short noncoding RNA (length ~ <200 bp), which regulate gene expression through binding to the 3ʹ‐untranslated region (3ʹ‐UTR) of target RNA transcripts and either degrade or repress their activities. In the latest research on EBV, it was found that this virus could encode miRNAs. Mechanistically, EBV‐encoded miRNAs are involved in carcinogenesis and the progression of EBV‐associated malignancies. Moreover, these miRNAs implicated in immune evasion, identification of pattern recognition receptors, regulation of lymphocyte activation and lethality, modulation of infected host cell antigen, maintain of EBV infection status, promotion of cell proliferation, invasion and migration, and reduction of apoptosis. As good news, not only has recent data demonstrated the crucial function of EBV‐encoded miRNAs in the pathogenesis of EBVaGC, but it has also been revealed that aberrant expression of exosomal miRNAs in EBVaGC has made them biomarkers for detection of EBVaGC. Regarding these substantial characterizes, the critical role of EBV‐encoded miRNAs has been a hot topic in research. In this review, we will focus on the multiple mechanisms involved in EBVaGC caused by EBV‐encoded miRNAs and briefly discuss their potential application in the clinic as a diagnostic biomarker.