幽门螺旋杆菌感染下, AEG-1核转位抑制自噬促进胃癌进展的分子机制研究

Helicobacter pylori (H. pylori) keeps persistent infection in gastric cancer tissue and promotes tumor progression. But the exact mechanism remains to be elucidated. Our previous study showed that H. pylori infection was an independent risk factor for gastric cancer. We proved that the nuclear translocation of AEG-1 correlate with H. pylori infection in gastric cancer tissue, which can promote the TLR4/NF-kappa B pathway with positively feed-back mechanism and amplify the inflammation process. Previous reports showed that both H. pylori infection and AEG-1 play roles in regulating tumor autophagy to exert their tumor-promoting effect. Recently, our preliminary experiments suggested that the nuclear translocation of AEG-1 was negatively correlated with autophagy level in gastric cancer. Therefore, we propose a new mode in the promotion of gastric cancer with H. pylori infection: The nuclear translocation of AEG-1 promotes gastric cancer progression by inhibiting autophagy activity in gastric cancer patients with H. pylori infection. This project intends to explore the correlation between nuclear translocation of AEG-1 and autophagy activity in gastric cancer with H. pylori infection. We will prove that the nuclear translocation of AEG-1 play key roles in inhibiting autophagy activity in gastric cancer with H. pylori infection. Finally, we will try to clarify the molecular mechanism how nuclear translocation of AEG-1 regulate the autophagy level in gastric cancer and testify it with animal experiment. This project aims to reveal a new mechanism about the autophagy regulation in gastric cancer with H. pylori infection, which could provide new strategy and theoretical foundation in the treatment of advanced gastric cancer.

幽门螺旋杆菌（H. pylori）在胃癌组织中持续感染并促进肿瘤进展，但机制不明。我们前期研究发现H. pylori可以通过癌基因AEG-1正反馈TLR4/NF-kB信号通路放大炎症效应；并证实H. pylori感染胃癌组织中AEG-1存在明显核转位。既往报道H. pylori感染和AEG-1均可参与调控肿瘤自噬实现其促癌进展效应。我们预实验亦发现AEG-1核转位与胃癌中自噬水平呈负相关。由此，我们提出H. pylori感染下胃癌进展的新机制：AEG-1核转位抑制自噬促进胃癌的进展。本项目拟首先观察幽门螺旋杆菌感染胃癌组织中AEG-1核转位与自噬水平的关系；继而证实AEG-1核转位是H. pylori感染下胃癌自噬受到抑制的关键；最后明确AEG-1核转位调控胃癌自噬水平的分子机制并在动物模型中验证。本研究有望揭示幽门螺旋杆菌致胃癌中自噬调控的新机制，为治疗进展期胃癌提供新的思路和理论依据。

幽门螺旋杆菌（H. pylori）在胃癌组织中持续感染并促进肿瘤进展，但机制不明。我们前期研究发现H. pylori可以通过癌基因AEG-1正反馈TLR4/NF-kB信号通路放大炎症效应；并证实H. pylori感染胃癌组织中AEG-1存在明显核转位。既往报道H. pylori感染和AEG-1均可参与调控肿瘤自噬实现其促癌进展效应。我们预实验亦发现AEG-1核转位与胃癌中自噬水平呈负相关。由此，我们提出H. pylori感染下胃癌进展的新机制：AEG-1核转位抑制自噬促进胃癌的进展。本项目拟首先观察幽门螺旋杆菌感染胃癌组织中AEG-1核转位与自噬水平的关系；继而证实AEG-1核转位是H. pylori感染下胃癌自噬受到抑制的关键；最后明确AEG-1核转位调控胃癌自噬水平的分子机制并在动物模型中验证。本研究有望揭示幽门螺旋杆菌致胃癌中自噬调控的新机制，为治疗进展期胃癌提供新的思路和理论依据。