EBV 通过 TRAF2 和 ERK 信号通路下调 EBV 相关胃癌中的 COX-2 表达。
EBV down-regulates COX-2 expression via TRAF2 and ERK signal pathway in EBV-associated gastric cancer.
机构信息
Department of Medical microbiology, School of Basic Medicine, Qingdao University, 38 Dengzhou Road, Qingdao, 266021, China.
Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, 19 Jiangsu Road, Qingdao, 266021, China.
出版信息
Virus Res. 2019 Oct 15;272:197735. doi: 10.1016/j.virusres.2019.197735. Epub 2019 Aug 29.
Epstein-Barr virus-associated gastric cancer (EBVaGC) accounts for nearly 10% of gastric cancer. Cyclooxygenase-2 (COX-2) plays a crucial role in cancer progression. However, there is no experimental study on the regulation mechanism of EBV on COX-2 in EBVaGC. To understand more about the tumorigenic mechanism of EBVaGC, the study investigated the role of EBV encode latent membrane protein LMP1 and LMP2A in the regulation of COX-2. The expression of COX-2 was examined in EBVaGC and EBV negative gastric cancer (EBVnGC) cell lines. The plasmids were transfected in SGC7901 to overexpress LMP1/2A. Small interfering RNA (si-RNA) targeting LMP1/2A in GT38 and targeting TRAF2 in SGC7901 were used to detect the expression of COX-2. Furthermore, si-ERK1/2 and the MEK inhibitor PD0325901 were used to investigate whether p-ERK participate in the regulation of COX-2 in SGC7901. The overexpression of LMP1 or LMP2A in SGC7901 down-regulates both COX-2 and TRAF2 expression, and knockdown of LMP1 or LMP2A in GT38 resulted in a certain recovery of COX-2 and TRAF2 expression. Moreover, si-TRAF2 indicated that a sharp down-regulation of COX-2. And the decrease of p-ERK also mediates the inhibitory effect of LMP1 on COX-2. In summary, overexpression of LMP1 and LMP2A inhibits COX-2, which is mediated by a decrease of TRAF2, and p-ERK is involved in the inhibition of COX-2 by LMP1 in gastric cancer.
EB 病毒相关胃癌（EBVaGC）约占胃癌的 10%。环氧化酶-2（COX-2）在癌症进展中起着关键作用。然而，目前尚没有关于 EBV 在 EBVaGC 中对 COX-2 调节机制的实验研究。为了更深入地了解 EBVaGC 的致癌机制，本研究探讨了 EBV 编码的潜伏膜蛋白 LMP1 和 LMP2A 在 COX-2 调节中的作用。检测了 EBVaGC 和 EBV 阴性胃癌（EBVnGC）细胞系中 COX-2 的表达。将质粒转染到 SGC7901 中以过表达 LMP1/2A。用针对 LMP1/2A 的 GT38 和针对 TRAF2 的 SGC7901 的 si-RNA 来检测 COX-2 的表达。此外，用 si-ERK1/2 和 MEK 抑制剂 PD0325901 来研究 p-ERK 是否参与 SGC7901 中 COX-2 的调节。LMP1 或 LMP2A 在 SGC7901 中的过表达下调了 COX-2 和 TRAF2 的表达，而 GT38 中 LMP1 或 LMP2A 的敲低导致 COX-2 和 TRAF2 的表达有一定程度的恢复。此外，si-TRAF2 表明 COX-2 的表达急剧下调。p-ERK 的减少也介导了 LMP1 对 COX-2 的抑制作用。总之，LMP1 和 LMP2A 的过表达抑制 COX-2，这是通过 TRAF2 的减少介导的，p-ERK 参与了 LMP1 在胃癌中对 COX-2 的抑制作用。
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