Department of Pathogenic Biology, Qingdao University Medical College, 38 Dengzhou Road, Qingdao, 266021, China.
Department of Pathology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
Virology. 2019 Aug;534:87-95. doi: 10.1016/j.virol.2019.06.006. Epub 2019 Jun 12.
Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a unique type of gastric carcinomas that promoter hypermethylation of tumor-related genes is extremely frequent to be found. Aquaporin 3 (AQP3) is a small membrane transport protein that plays a crucial role in cancer progression and metastasis. However, there is no experimental study on the expression of AQP3 in EBVaGC and the regulation mechanism of EBV on AQP3. In this study, the loss of AQP3 was contributed by the hypermethylation status of AQP3 promoter in EBVaGC which was caused by elevated expression of DNMT3a. In addition, stable and transient transfection system in SGC7901 showed that viral latent membrane protein 2A (LMP2A) activated phosphorylated ERK and up-regulated DNMT3a. Taken together, LMP2A induced the phosphorylation of ERK, which activated DNMT3a transcription and caused AQP3 expression loss through CpG island methylation of AQP3 promoter in EBVaGC.
EBV 相关胃腺癌（EBVaGC）是一种独特类型的胃腺癌，其肿瘤相关基因的启动子高甲基化极为常见。水通道蛋白 3（AQP3）是一种小的膜转运蛋白，在癌症进展和转移中起着关键作用。然而，目前还没有关于 AQP3 在 EBVaGC 中的表达以及 EBV 对 AQP3 调节机制的实验研究。在这项研究中，AQP3 的缺失是由于 EBVaGC 中 AQP3 启动子的高甲基化状态所致，这是由 DNMT3a 的表达升高引起的。此外，在 SGC7901 中稳定和瞬时转染系统表明，病毒潜伏膜蛋白 2A（LMP2A）激活磷酸化 ERK，并上调 DNMT3a。总之，LMP2A 诱导 ERK 的磷酸化，通过 AQP3 启动子的 CpG 岛甲基化激活 DNMT3a 转录，导致 EBVaGC 中 AQP3 的表达缺失。
