基于前期研究结果，即发现幽门螺杆菌（HP）与MDM2交互作用可增加胃癌发生的风险（Helicobacter, 2009,14:114-9），HP的毒力因子LPS能增加野生型和突变型MDM2启动子的活性，且受到SDF1/CXCR4效应轴的调控（已投稿至Cancer杂志），我们进而研究MDM2在HP致胃上皮细胞病变中的下游分子机制。预实验发现，高表达MDM2可以抑制P63继而使Dicer酶活性降低，HP-LPS能下调miRNA106b的表达，也能下调Dicer酶的表达。因而我们提出Hp-LPS通过MDM2/P63-Dicer酶途径下调miRNA106b的科学假说，本项目拟利用RNA干扰、ChIP分析、报告基因分析、EMSA、细胞迁移实验等手段，来阐明MDM2/P63-Dicer酶途径对miRNA106b的调控机制及其在HP致病中的作用，为HP感染引起胃粘膜病变的分子机制提供新的理论依据。

Based on the results of preliminary studies, which the interaction between Helicobacter pylori (HP) and MDM2 increased the risk of gastric cancer (Helicobacter, 2009,14:114-9), HP virulence factor LPS can increase the wild type and mutant MDM2 promoter activity via the SDF1/CXCR4 axis, we further study the downstream molecular mechanisms of MDM2 in HP induced gastric epithelial cell lesions. Preliminary experiments found that high expression of MDM2 can inhibit the P63 and then decrease the activity of the Dicer enzyme. LPS can decrease not only the miRNA106b expression, but also the expression of the Dicer enzyme. Thus we put forward a scientific hypothesis that Hp-LPS decrease miRNA106b via the MDM2/P63-Dicer enzymatic pathways. By us of RNA interference, ChIP assay, Reporter assay, EMSA, and cell migration assay, etc., this project will confirm that the miRNA106b regulation is via MDM2/P63-Dicer pathway, which plays role in pathogenesis of Helicobacter pylori. It will provide a new theoretical basis for the molecular mechanism of gastric mucosal lesions caused by HP infection.