HCMV IE1基因调控DTX3L通路促进胃癌转移的作用及机制研究

肿瘤侵袭转移是导致胃癌死亡主要原因，但其机制尚未阐明。我们前期证实，人巨细胞病毒（HCMV）感染能够促进胃癌转移。HCMV IE1基因又称UL123基因，可以通过宿主DTX3L基因互作参与了HCMV促进胃癌转移的过程。本项目进一步IE1基因介导DTX3L通路促进胃癌转移的作用及机制。通过体内外实验及整病毒IE1干预实验，明确IE1是HCMV促进胃癌转移的关键基因；在稳转IE1的胃癌细胞中调控DTX3L的表达，明确DTX3L在IE1生物学效应中的作用。采用免疫共沉淀、酵母双杂交技术等技术明确IE1与DTX3L的调节关系及其下游信号通路。最后通过诱导沉默及过表达技术，在细胞学水平及动物体内水平评价IE1-DTX3L轴及其下游信号通路的生物学效应。本项目的开展将进一步明确HCMV感染与胃癌的关系及机制，为胃癌防治策略提供新的思路。

Tumor invasion and metastasis are the main causes of gastric cancer death, its mechanism has not been clarified. We have previously confirmed that human cytomegalovirus (HCMV) infection can promote the metastasis of gastric cancer, IE1 which is named UL123 gene may be involved in the process of HCMV promoting gastric cancer metastasis through the interaction of host DTX3L gene. This project further explores the role and mechanism of IE1-mediated DTX3L pathway in promoting the metastasis of gastric cancer. Vitro and vivo experiment and IE1 intervention of whole virus were performed to identified the key role of IE1 in promoting gastric cancer metastasis and to explore the regulation of DTX3L expression in gastric cancer cells stabilizing IE1, thus clarified the role of DTX3L in the biological effects of IE1. Immunoprecipitation and yeast two-hybrid techniques were further performed to identify the regulatory relationship between IE1 and DTX3L and its downstream signaling pathway. Finally, the biological effects of IE1-DTX3L axis and its downstream signaling pathway were evaluated by induced silence and overexpression techniques. This project will further clarify the relationship and mechanism between HCMV infection and gastric cancer, and provide new ideas for the prevention and treatment of gastric cancer.