BRD7与细胞周期蛋白CDC5L相互作用的机制及其在结直肠癌中的意义

结直肠癌是最常见、预后差的恶性肿瘤之一，主要以手术和放化疗为主的综合治疗，但其发病机制仍然不明。我们前期研究发现：BRD7在结直肠癌中呈低水平表达，且与临床分期显著负相关，可作为结直肠癌患者的独立预后因子。最近的预实验结果表明：细胞周期蛋白CDC5L可与BRD7相互作用，并抑制BRD7的转录活性。敲低CDC5L则促进BRD7下游靶基因的表达。这些结果提示：CDC5L可能通过负调控BRD7发挥癌基因的功能。本项目拟采用免疫荧光、免疫共沉淀（Co-IP）、GST-Pull down、细胞同步化等方法，进一步研究BRD7与CDC5L相互作用的分子机制、及对各自功能的影响，并用临床结直肠癌标本，探讨CDC5L在结直肠癌预后中的作用、其表达是否与BRD7表达呈负相关。本项目的开展将有助于阐明结直肠癌的发病机制，也可能为结直肠癌的诊断与靶向治疗提供新的思路。

Colorectal cancer is one of the most common malignant tumors with poor prognosis, and its pathogenesis still keeps unknown. Operation and chemotherapy are mainly comprehensive treatment for this disease. Our previous study indicated that BRD7 expression was lower in colorectal cancer compared to normal tissue, and its expression level was significantly negative correlated with clinical stage. Univariate and multivariate analyses indicated that BRD7 expression was an independent prognostic factor for patients with colorectal cancer. Our recent study found that: 1) CDC5L interacted with BRD7; 2) Overexpression of CDC5L inhibited BRD7 transcriptional activity; 3) Knock-down of CDC5L promotes the expression of BRD7 downstream target genes. These results suggested that CDC5L may function as an oncogene through negative regulation of BRD7. In this project, multiple methods, including immunofluorescence, Co-IP, GST-Pull down, cell synchronization,will be performed to further elucidate the molecular mechanism of BRD7 interaction with CDC5L and to explore the biological function changes after interacting between the two proteins.We will detect the expression of CDC5L in colorectal tissues and analyse its potential role in colorectal cancer development. Taken together, This study would help to further understand the mechanism of tumorigenesis and identify a novel potential target for dignosis and therapy in colorectal cancer.