肿瘤干细胞内在的耐药性与肿瘤患者的生存预后及复发密切相关。因此探讨肿瘤干细胞特性的调控机制及寻找分子靶点至关重要。前期我们已发表文章证实TRIM37在胰腺癌中高表达并促进肿瘤增殖及转移。近期通过公共数据库及临床胰腺癌样本分析我们发现TRIM37高表达可促进胰腺癌的耐药和复发。进一步体内外预实验结果显示：高表达TRIM37可①促进肿瘤细胞对化疗药物5-FU的耐药性；②增强胰腺癌肿瘤干细胞特性。这些结果表明TRIM37具有增强胰腺癌耐药的生物学功能。结合公共数据库分析、双荧光酶报告基因系统及染色体免疫共沉淀等方法，我们还发现：TRIM37①通过单泛素化H2A而激活TGF-β信号通路；②通过NEMO-K63位泛素化及IκBа-K48位泛素化而激活NF-κB信号通路。因此，本研究将进一步探索TRIM37增强胰腺癌肿瘤干细胞及肿瘤耐药的分子机制，为胰腺癌的治疗和预后提供新的分子靶点及诊断标记物。

Chemoresistance, a vital characteristic of cancer stem cells (CSCs), is closely related to the prognosis and recurrence of cancer. Therefore, it is important to study the regulatory mechanism of CSCs and to search for molecular targets for cancer treatment. We have confirmed that TRIM37 is up-regulated in pancreatic cancer, which enhances tumor growth and metastasis. Recently, by analyzing public databases and clinical samples, we found that TRIM37 accelerates chemoresistance and recurrence of pancreatic cancer. Further in vivo and in vitro experiments showed TRIM37 enhances the characteristics of pancreatic CSCs and promotes the capacity of chemoresistance to 5-FU. Combined with public database analysis, dual luciferase assays and ChIP, we also found TRIM37 activates TGF-β signaling by H2A mono-ubiquitin, and activates NF-κB signaling by NEMO-K63 and IκBа -K48 ubiquitin. In current project, we would analyze the molecular mechanisms of TRIM37 that promotes CSC-like traits and chemoresistance in pancreatic cancer, which will provide new molecular targets and diagnostic markers for the treatment and prognosis of pancreatic cancer.