USP39属于泛素蛋白酶家族但不具蛋白酶活性，被认为是一种与肿瘤关系密切的剪接相关因子，但其在肠炎及恶变中的功能不清。我们前期发现在肠炎恶变及癌组织中USP39表达递增，且能调控NOD1/2/NF-κB/STAT3、p53通路。本项目是以条件性USP39基因敲除小鼠、Apcmin/+/；USP39-/-小鼠采用化学诱导急性炎症及相关肠癌、USP39-/-肠上皮细胞、结肠癌细胞为研究对象，1）明确USP39在调控肠炎发生和肠炎恶变过程中所介导的生物学功能；2）重点靶向NOD1/2/NF-κB/STAT3、p53通路，阐明USP39调控肠炎及其恶变过程中的分子机制，并进一步采用cDNA芯片、质谱、RIP、Co-IP等筛选并鉴定USP39参与的其他通路；3）结合临床肠炎及肠癌标本进行验证及临床意义分析，寻找包括USP39在内可能的分子作为慢性肠炎恶变的标志物，为其临床应用奠定理论基础。

Ubiquitin Specific Peptidase 39 (USP39), possessing no proteinase activity as a member of ubiquitin protease family, is considered to be a splicing factor and associated deeply with the development of tumor. However, its functions in occurrence and deterioration of colitis are still unclear. Our previous studies reveal that the expression of USP39 is increased progressively with a regulation of NOD1/2, NF-κB /STAT3, and p53 pathway in malignant colitis and colon cancer tissues. This project will take full advantages of usp39 conditional knockout mice, Apcmin/+/usp39-/- mice, chemical-induced acute inflammation and its cancer-associated animal models, usp39-/- colon epithelial cells and cancer cells as our research objects, to 1) confirm the biological functions of usp39 in regulating colitis occurrence and facilitating colitis deterioration; 2) aim at key signaling pathways, such as NOD1/2, NF-κB /STAT3, and p53 pathway, elucidate the molecular mechanism of USP39 in regulating colitis and its process of malignant transformation, then further screen and identify other pathways that USP39 involves in through co-immunoprecipitation (Co-IP), RNA Binding Protein Immunoprecipitation (RIP), cDNA chip and liquid chromatography–mass spectrometry (LC-MS); 3) test and verify related molecular mechanism and do clinical significance analysis by combining with colitis and colon cancer tissues from clinical patients, search for potential markers of deterioration of chronic colitis including USP39, and lay a theoretical foundation for its application in clinical therapy.