幽门螺杆菌（Hp）分泌的CagA是导致胃上皮细胞产生炎性反应及癌变的重要蛋白，抑制其效应是目前的研究热点。课题组已证实牙髓卟啉单胞菌（Pe）在胃癌患者胃液富集，但其对Hp介导胃炎及胃癌的作用机制不详。文献及预实验提示SHP1是拮抗CagA的磷酸酶且Pe通过调控胃上皮细胞SHP1甲基化抑制其表达。课题组芯片证据显示Lnc-AC093817在Pe感染的上皮细胞中高表达且负向调控SHP1。信息学预测该Lnc与SHP1甲基转移酶DNMT1存在结合关系。故提出“Pe调控胃上皮细胞Lnc-AC093817/DNMT1/SHP1甲基化轴促进Hp/CagA细胞毒性”假说。本课题拟通过体内外实验证实Pe调控LncRNA及SHP1促进Hp/CagA细胞毒效应，利用RIP、ChIP等技术阐明该Lnc对SHP1甲基化的调控细节，并采用动物模型确认干预该路径对Pe/Hp协同作用的影响，以期为胃癌的防治提供新思路。

CagA secreted by Helicobacter pylori (Hp) is an essential protein that causes inflammatory reactions and carcinogenesis in gastric epithelial cell. The inhibition of its effects is presently a research hotspot. Our group has confirmed that Porphyromonas endodontalis (Pe) is enriched in gastric juice in patients with gastric cancer, but its role and mechanism on Hp mediated gastritis and gastric cancer is unknown. The literature and preliminary experiments suggest that SHP1 is a phosphatase that antagonizes CagA. In addition, Pe inhibits SHP1 expression by regulating its methylation in gastric epithelial cells. The microarray showed that Lnc-AC093817 is highly expressed in Pe infected epithelial cells and negatively regulates SHP1 expression. Bioinformatics analysis predicts that Lnc-AC093817 can bind to DNMT1 which is the methyltransferase of SHP1. Therefore, we hypothesized that Pe regulates Lnc-AC093817 / DNMT1 / SHP1 methylation axis in gastric epithelial cells to encourage Hp / CagA cytotoxicity. This research aims to clarify that Pe regulates LncRNA and SHP1 expression to promote Hp / CagA cytotoxicity by in vitro and in vivo experiments, to elucidate the regulatory details of Lnc-AC093817 on SHP1 methylation by RIP, ChIP and other techniques, and to confirm the effect of this pathway on Pe / Hp synergism by animal models, which would provide new ideas for the prevention and treatment of gastric cancer.