胃类器官（organoid）是一种新的研究载体，在体外高度模拟胃内微环境，但是HP损伤胃organoid的机制鲜有报道。前期研究中，我们在细胞水平发现HP可以通过NF-κB诱导P53上调凋亡调控因子（PUMA），从而促进胃粘膜炎症的发生发展；随后，我们拟用胃organoid模型来探寻其机制，在成功建立HP感染胃organoid模型的基础上，通过芯片筛选、数据库分析，发现HPlnc1在HP阳性胃organoid中有明显的高表达，其可结合miR-520，调控p65。据此，我们提出HPlnc1竞争性结合miR-520，减少p65降解、增加NF-ĸB的活性，从而激活PUMA，启动caspase通路，促进胃organoid损伤的科学假说。本项目拟利用转基因鼠、CHIP、RNA pull-down等手段，从lncRNA与胃organoid关系的新视角探讨HP致病机制，为HP相关性疾病的防治提供新思路。

Gastric organoid is a new model which can simulate gastric environment in vitro, but few study has be conducted about Helicobacter pylori (HP) and gastric organoid. We found HP could activate PUMA via NF-κB in cells and lead to gastritis. Then we plan to illuminate the mechanism in gastric organoid. We cultured HP infected gastric organoid and found that lncRNA HPlnc1 was upregulated and could interact with miR-520, regulating its target p65 . Thus we put forward a scientific hypothesis that lncRNA HPlnc1 activates PUMA, and caspase apoptosis pathway via targeting miR-520. By use of transgenic mice, CHIP, RNA pull down, etc., this project will uncover the role of lncRNA HPlnc1 in gastric organoid injured by HP and provide new molecular mechanism and therapy target.