胆囊癌是胆道系统最常见的恶性肿瘤，早期诊断困难且易发生侵袭转移，预后极差，故亟需探索有效的分子靶点。我们在前期工作中，发现转录因子E2F1和E2F7在转录水平上共同调控胆囊癌癌基因KPNA2的表达，并且E2F7的二聚化位点在其细胞定位、自身表达和发挥功能上起着非常重要的作用。为了进一步研究其分子机制，我们应用免疫共沉淀和质谱分析筛选了一系列通过E2F7二聚化位点与之结合的蛋白，并锁定了一个靶蛋白NONO。我们提出假说，E2F7通过与NONO结合，增强E2F7与启动子的亲和力，从而改变E2F7的转录调控。本课题拟从分子、细胞水平揭示NONO影响E2F7转录调控的机制，为深入研究E2F7在胆囊癌中的功能机制以及NONO的肿瘤生物学功能的提供基础。

Gallbladder carcinoma is the most common malignant tumor in biliary system. The prognosis of the disease is very poor because it is difficult to diagnose at the early stage and prone to invasion and metastasis. it is urgent to explore new effective molecular targets. Our previous study found that transcription factors E2F1 and E2F7 collaboratively and differently regulate oncogene KPNA2 expression in gallbladder cancer, and the heterodimerization contacts of E2F7 play important roles in E2F7 cell distribution, expression and functions. To further study its molecular mechanism, we applied co-immunoprecipitation and mass spectrometry to screen a series of proteins bound to E2F7 through heterodimerization contacts, and chose NONO as one target protein. We then propose a hypothesis that E2F7 binds NONO to enhance the affinity of E2F7 on the promoter, thereby altering E2F7 transcriptional regulation function. This study intends to reveal the mechanism by which NONO affects the transcriptional regulation of E2F7 at molecular and cellular level, and provide a basis for further research on the functions and mechanism of E2F7 in gallbladder cancer and the tumor biological function of NONO.