Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Cell Physiol. 2021 Sep;236(9):6136-6153. doi: 10.1002/jcp.30297. Epub 2021 Jan 28.
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 3'-untranslated region (3'-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.
EB 病毒(EBV)相关胃癌(EBVaGC)被认为是最常见的由 EBV 感染引发的恶性肿瘤。近年来,人们越来越关注对该疾病过程的确切机制有更深入的认识。越来越多的证据表明,表观遗传修饰在 EBVaGC 的发病机制中起着关键作用。miRNAs(miRNAs)作为重要的表观遗传调节剂,是单链短非编码 RNA(长度~<200bp),通过与靶 RNA 转录物的 3'-非翻译区(3'-UTR)结合来调节基因表达,从而降解或抑制其活性。在最近对 EBV 的研究中,发现该病毒可以编码 miRNAs。从机制上讲,EBV 编码的 miRNAs 参与了致癌作用和 EBV 相关恶性肿瘤的进展。此外,这些 miRNAs 还参与免疫逃逸、模式识别受体的鉴定、淋巴细胞激活和致死性的调节、感染宿主细胞抗原的调节、EBV 感染状态的维持、促进细胞增殖、侵袭和迁移,以及减少细胞凋亡。好消息是,不仅最近的数据表明 EBV 编码的 miRNAs 在 EBVaGC 的发病机制中具有重要作用,而且还揭示了 EBVaGC 中外泌体 miRNAs 的异常表达使其成为检测 EBVaGC 的生物标志物。鉴于这些显著的特征,EBV 编码的 miRNAs 的关键作用已成为研究的热点。在这篇综述中,我们将重点讨论 EBV 编码的 miRNAs 引起 EBVaGC 的多种机制,并简要讨论它们作为诊断生物标志物在临床中的潜在应用。