肝内胆管癌（ICC）是恶性程度最高的肿瘤之一，其发生与大量基因转录重编程密切相关。BRG1作为染色体重构复合物SWI/SNF的关键亚基，介导了重编程过程。BRG1的突变或缺失被证实与肿瘤发生密切相关，因此被定义为抑癌基因。然而在ICC组织中，我们发现BRG1高表达，其缺失反而抑制了TAA诱导小鼠ICC的发生，提示BRG1在ICC发生过程中并不发挥肿瘤抑制作用，相反促进了ICC的发生。进一步分析，我们发现细胞周期关键调控因子DBF4与BRG1具有相同的表达模式，在BRG1敲除小鼠肝脏中表达显著降低，沉默DBF4可抑制胆管癌细胞的增殖。因此我们推测DBF4介导了BRG1促ICC的发生过程。本研究将利用临床样品、转基因小鼠模型结合体内外实验，以期证明BRG1通过上调DBF4的表达促ICC的发生，同时阐明其中所涉及的分子机制，为揭示ICC的发生发展机制提供线索，为ICC的临床诊治提供理论基础。

Intrahepatic cholangiocarcinoma (ICC) is one of the most malignant tumors and is closely related to gene transcription reprogramming. As a key subunit of the chromosome remodeling SWI/SNF complex, BRG1 mediates the reprogramming process and participates in comprehensive gene expression regulation. Its mutation or deletion is closely related to tumorigenesis. Surprisingly, our previous study found that BRG1 is highly expressed in ICC tissues, and its liver-specific ablation inhibits TAA-induced ICC development in mice, suggesting that unlike other tumors, high expression of BRG1 instead of deficiency promotes ICC occurrence. Furthermore, we found that DBF4, a key regulator of cell cycle, has the same expression pattern as BRG1, and it is significantly decreased in BRG1 knockout mice. Meanwhile silencing of DBF4 can inhibit the proliferation of cholangiocarcinoma cells. Therefore, we speculate that DBF4 mediates the process of BRG1 promoting ICC. This study will use clinical samples, transgenic mouse models combined with in vitro and in vivo experiments to demonstrate the role of BRG1 and DBF4 in the development of ICC, and to elucidate the molecular mechanisms involved, which can enrich the theoretical basis of cholangiocarcinoma.