炎症性肠病是结肠癌的诱因之一，其中，免疫调节异常是介导炎症失控、进而诱导肿瘤发生的关键。为此，我们通过构建小鼠肠炎癌转化模型开展免疫调控研究，发现microRNA15a/16-1(miR-15/16)是一个关键调控分子，表现为：1) miR-15/16缺陷促进小鼠肠炎癌转化；2) miR-15/16缺失上调肠道B细胞的比例，促进其在肠道内富集；3) miR-15/16缺失后B细胞活力增强，TGF-β分泌增加。提示，miR-15/16在肠炎癌转化中具有负向调控作用，且与B细胞相关。因此，本项目拟利用miR-15/16和B细胞敲除鼠，联合miR-15/16体内外过表达，B细胞体内过继转输及功能检测，生物信息预测及蛋白质组学分析等技术方法，进一步明确miR-15/16调控的关键免疫细胞及分子，解析其在肠炎癌转化中的具体作用及机制，期望为有效控制炎症反应的强度、缓解肿瘤发生，提供理论和实验依据。

Inflammatory bowel disease (IBD) increases the risk of colon cancer. Large amounts of cytokines and immune cells are enriched in intestine tissue, which is crucial in the non-resolving intestinal inflammation and it associated tumorigenesis. In our previous studies, we investigated the immune regulation by establishing the animal model of IBD associated cancer induced by azoxymethane (AOM) and dextran sulfate sodium salt (DSS), and found that the small non-coding RNAs--microRNA (miRNA), miR-15/16 functioned as important regulators. The results showed that deficiency of miR-15/16 in mice promoted the development of IBD associated cancer, with increased accumulation of B-lymphocytes in intestine tissue. Moreover, B-lymphocytes with miR-15/16 deficiency had increased cell activation and more TGF-beta secretion. These data indicates miR-15/16 may be function as a suppressor during IBD associated neoplastic transformation, and B cell was involved in this process. Therefore, this project is designed to investigate the key immune cells and molecules under the regulation of miR-15/16 on the transformation, and clarify the mechanism underlying by modulating the expression of miR-15/16 in B cell, performing B cell adoptive transfer, as well as using proteomics-and bioinformatics-associated techniques. This project may be provide the basics for controlling the inflammation and preventing IBD-associated colorectal cancer, and thereby improve the early diagnosis and prognosis of IBD transformation.