Xiangya Hospital, Department of Pathology, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 410008, China.
Xiangya Hospital, Department of Pathology, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, 410008, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, NHC Key Laboratory of Carcinogenesis, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Changsha, Hunan, China.
Biochem Biophys Res Commun. 2021 Apr 2;547:1-8. doi: 10.1016/j.bbrc.2021.02.014. Epub 2021 Feb 12.
Epstein-Barr virus (EBV) is the first identified human tumor-related DNA virus, and has a high infection among people worldwide. Recent studies have showed that nearly 10% of gastric cancers have shown EBV infection and this kind of gastric cancer has been identified as a new subtype: EBV associated Gastric cancer (EBVaGC). Furthermore, it has been reported that tumor related genes in the EBVaGC showed frequent methylation modifications compared to those in the EBV negative gastric cancer (EBVnGC). To fully understand the role of EBV in EBVaGC, we analyzed and found that 16.67% of gastric carcinoma samples showed positive EBER1 signals. Mechanically, EBV-encoded Latent membrane protein 1 (LMP1) inhibited the expression of RASSF10, and promoted tumorigenesis by recruiting DNMT1 and inducing the DNA methylation of RASSF10. Altogether, it allows us a better understanding of the possible mechanism of EBV-induced gene hypermethylation in gastric cancer genome. Targeting EBV-induced DNA methylation is a potential therapeutic modality of EBVaGC.
EB 病毒（EBV）是第一个被鉴定的与人类肿瘤相关的 DNA 病毒，在全球人群中具有较高的感染率。最近的研究表明，近 10%的胃癌显示出 EBV 感染，这种胃癌已被确定为一种新的亚型：EBV 相关胃癌（EBVaGC）。此外，据报道，与 EBV 阴性胃癌（EBVnGC）相比，EBVaGC 中的肿瘤相关基因表现出频繁的甲基化修饰。为了充分了解 EBV 在 EBVaGC 中的作用，我们进行了分析，发现 16.67%的胃癌样本显示出阳性 EBER1 信号。从机制上讲，EBV 编码的潜伏膜蛋白 1（LMP1）抑制 RASSF10 的表达，通过招募 DNMT1 并诱导 RASSF10 的 DNA 甲基化来促进肿瘤发生。总之，这使我们更好地了解 EBV 诱导的胃癌基因组中基因过度甲基化的可能机制。针对 EBV 诱导的 DNA 甲基化是 EBVaGC 的一种潜在治疗方法。
