胃粘膜肠化生是胃癌最重要的癌前病变，其发生机制尚不清楚。CDX1表达异常增高被认为与肠化生密切相关。我们前期研究发现肠上皮化生的组织中CDX1表达明显升高，并证明miR-296-5p在胃癌中通过靶向CDX1调控其表达。而肠化生的过程中miR-296-5p/CDX1通路发挥的调控作用尚无报道。本项目拟通过免疫印迹、PCR等方法在肠化生细胞模型中验证miR-296-5p和CDX1的表型；通过慢病毒载体、siRNA技术和扫描电镜等技术研究miR-296-5p调控肠化生的功能及CDX1对其功能的介导作用；利用免疫共沉淀、截断报告基因实验和免疫印迹等实验明确CDX1下游相关基因；并最终在临床肠化生组织标本中验证miR-296-5p和CDX1及其下游基因的相关关系。本项目旨在探索胃癌重要癌前病变-肠上皮化生过程中的分子调控机制，以期初步阐明miR-296-5p/CDX1通路在胃粘膜上皮肠化生中的作用。

Gastric intestinal metaplasia (IM) is the most important precancerous lesion of gastric carcinoma.It is reported that activation of CDX1,which is specifically expressed in intestinal epethelial cells, may be a key factor during the development of gastric intestinal metaplasia, but the mechanism remains to be fully elucidated. Our previous work confirmed CDX1 expression is upregulated in IM tissues. We also found that miR-296-5p inhibits SOX2 expression by directly binding to its 3’-UTR.However,the regulation of miR-296-5p/CDX1 pathway in the development of IM have not been elucidated. This project is going to explore the correlation of miR-296-5p and CDX1 expressions in IM cell model induced by bile acids using PCR and western blot;To investigate the functions of miR-296-5p and CDX1 in gastric IM in gain-of-function and loss-of-function model using lentiviral vector and siRNA;To explore the mechanism of CDX1 and its downstream genes through Ch-IP,EMSA, and luciferase reporter gene assay;To verify the relationship among miR-296-5p, CDX1,and its downstream genes in clinical IM tissues using in situ hybridization and immunohistochemisty.This project aims at elucidating the function and mechanism of miR-296-5p/CDX1 pathway in gastric IM, further understanding intestinal metaplasia on microRNA and transcriptional factor level, and offering theoretical and experimental proof for the diagnosis and treatment of gastric precancerous lesion.