幽门螺杆菌感染及其诱发的炎症促进胃粘膜组织恶性转化，但机制尚未阐明。我们研究发现从幽门螺杆菌感染引起的慢性胃炎到胃癌演进过程中，泛素连接酶底物结合蛋白FBXO31表达呈降低趋势，进一步研究证实幽门螺杆菌对FBXO31的表达抑制可促进细胞的恶性转化。因此，本课题从FBXO31介导的底物蛋白的泛素化降解视角解析幽门螺杆菌诱导胃粘膜组织恶性转化的机理。主要研究内容如下：①解析幽门螺杆菌抑制FBXO31表达的分子机制；确定FBXO31识别、结合的关键靶蛋白，明确FBXO31调控这些靶蛋白的分子机制以及幽门螺杆菌通过调控FBXO31及其下游靶蛋白促进细胞恶性转化的机理；②动物水平检测幽门螺杆菌感染引起胃粘膜病理改变与调控FBXO31及其下游分子网络的相关性；③临床组织水平验证FBXO31及其下游分子网络与幽门螺杆菌感染促进胃粘膜组织恶性转化的关系。为基于FBXO31为靶点的胃癌早期干预提供科学依据。

Infection and inflammation induced by Helicobacter pylori (H. pylori) contributed to the malignant transformation of gastric mucosa tissues.Our previous study results showed that ubiquitin ligase substrate binding protein FBXO31 can be gradually inhibited during the process of Helicobacter pylori-mediated chronic gastritis to gastric cancer. Furthermore,we found that the down-regulation of FBXO31 mediated by Helocobacter pylori infection promoted the malignant transformation of gastric epithelial cell; but the molecular mechanism has not yet been clarified.Therefore,this project investigates the molecular mechanism of gastric mucosa tissues malignant transformation induced by Helicobacter pylori from the perspective of FBXO31-mediated ubiquitin-proteasome degradation of substrate protein.Based on the recent research progress and our previous studies,the aim of this project is to make clear the following questions: (1) To investigate the molecular mechanism of Helicobacter pylori inhibiting FBXO31 expression；To screen and identify the key downstream target molecules of FBXO31 and further explore the regulatory mechanism of FBXO31 on the expression of these target molecules from molecular and cellular level.To elucidate the mechanism that Helicobacter pylori promoters the malignant transformation by regulating FBXO31 and its downstream target molecules network.(2) To detect the role of Helicobacter pylori promotes the malignant transformation of gastric mucosa tissues by regulating FBXO31 and its downstream target molecules network from the animal level.(3) To verify the correlations between FBXO31 and gastric cancer formation mediated by Helicobacter pylori from human pathological tissue levels .This study aims to provide the theory evidence for the hypothesis that FBXO31 can be used as a key point and therapeutic target in the early intervention of gastric cancer .