幽门螺杆菌调控circRNA m6A甲基化修饰介导胃黏膜上皮细胞恶性转化的机制研究

胃癌是中国高发恶性肿瘤之一，幽门螺杆菌感染是胃癌发生的重要始动因素，然而幽门螺杆菌介导胃黏膜细胞恶性转化的具体机制尚未阐明。circRNA m6A修饰在肿瘤中的作用目前是国际前沿研究领域，申请者首次通过MeRIP-seq和RNA-seq技术筛选出幽门螺杆菌调控发生m6A修饰的circRNA分子，并通过细胞分子生物学实验发现circMAN1A2 m6A修饰在幽门螺杆菌介导恶性转化过程中发挥重要作用。本项目拟在前期基础上研究：（1）幽门螺杆菌介导circMAN1A2 m6A修饰促进胃黏膜上皮细胞恶性转化的分子机制；（2）在动物整体水平确定circMAN1A2 m6A修饰与胃黏膜恶性转化的关联及其在体内对肿瘤生长的作用；（3）在人体胃组织标本中检测相关分子的表达，明确circMAN1A2 m6A修饰与幽门螺杆菌感染胃黏膜细胞恶性转化的相关性。旨在为胃癌的干预和分子标志物的开发提供新思路和新靶点。

Gastric cancer is one of the most common malignant tumors in China. Helicobacter pylori infection is an important initiating factor for gastric cancer development. However, the specific mechanism of Helicobacter pylori infection mediated malignant transformation of gastric mucosal cells has not yet been elucidated. The study of the role of circRNA m6A methylation in tumors is currently a frontier of medical research. For the first time, the applicant has screened out Helicobacter pylori regulated circRNAs modified with m6A through MeRIP-seq and RNA-seq technology, and found that circRNA m6A modification plays an important role in the malignant transformation induced by Helicobacter pylori infection. This project intends to study:(1) the molecular mechanism of Helicobacter pylori-mediated m6A modification of circMAN1A2 to promote malignant transformation of gastric mucosal epithelial cells; (2) the relationship between circMAN1A2 m6A and the malignant transformation of gastric mucosa in Helicobacter pylori infected animals and the effect of circMAN1A2 m6A on tumor growth in vivo; (3) the correlation between circMAN1A2 m6A modification and malignant transformation of gastric mucosal cells infected by Helicobacter pylori by detecting the expression of related molecules in human gastric tissue specimens. The research aims to provide novel ideas and strategies for the intervention of gastric cancer and development of biomarkers for gastric cancer.