Study of mechanism of gastric carcinogenesis associated with EBV-mediated IGF-1 induction

我们以前曾报道，EBV感染的胃上皮细胞导致诱导胰岛素样生长因子（IGF）-1和IGF-1促进EBV感染的细胞的生长通过自分泌机制。我们还确定了EBV编码的小RNA（EBER）是IGF-1诱导的负责基因。在这项研究中，我们证明了EBV通过EBER诱导IGF-1促进鼻咽上皮细胞的生长。此外，我们观察到IGF-1在鼻咽癌组织中的高表达。这些发现强烈表明，EBER在上皮癌的发展中起着重要作用。我们还试图评估EBER介导的IGF-1诱导机制，并确定EBER通过与视黄酸诱导基因（RIG）-I相互作用诱导细胞内信号传导（已提交）。由于RIG-I具有RNA解旋酶结构域和半胱天冬酶激活和募集结构域（CARD），其识别dsRNA并通过激活IRF-3或NF-κB诱导干扰素和其它细胞因子的产生。我们的研究结果表明，EBER-RIG-I相互作用诱导EBV感染的细胞中生长因子的表达，进一步的研究正在进行中。

We have previously reported that EBV infection of gastric epithelial cells leads to induction of insulin-like growth factor (IGF)-1 and IGF-1 promotes growth of EBV-infected cells by an autocrine mechanism. We have also identified that EBV-encoded small RNA (EBER) is the responsible gene for IGF-1 induction. In this study, we demonstrated that EBV promotes growth of nasopharyngeal epithelial cells thorough induction of IGF-1 by EBER. Furthermore, we observed high IGF-1 expression in nasopharyngeal carcinoma (NPC) tissues. These findings strongly suggest that EBER plays a significant role in epithelial cancer development. We also tried to assess the mechanism of EBER-mediated IGF-1 induction and identified that EBER induces intracellular signaling through interaction with retinoic acid-inducible gene (RIG)-I (Submitted). Since RIG-I has RNA-helicase domain and Caspase activation and recruiting domain (CARD), it recognizes dsRNA and induces production of interferon and other cytokines through activation of IRF-3 or NF-κB. Our results suggest that EBER-RIG-I interaction induces growth factor expression in EBV-infected cells, and further study is going on.