叉头框蛋白M1(FOXM1)通过转录激活存活素(survivin)基因表达而参与结肠癌肝转移表型形成的分子机制研究

结肠癌肝转移是结肠癌最常见的转移类型，其形成过程涉及肿瘤转移相关蛋白基因表达及其调控的各个过程。FOXM1是叉头框转录因子家族重要成员之一，本课题组前期研究结果表明：结肠癌组织中FOXM1基因表达水平与患者临床分期、淋巴结转移状况及预后密切相关，但是其在结肠癌肝转移表型形成过程中的作用及其转录调控机制仍不清楚。在前期成功筛选结肠癌肝转移相关转录因子差异表达谱及生物信息学分析的基础上，本课题拟从细胞和活体动物水平进行FOXM1与结肠癌肝转移表型形成相关的功能学分析，并通过荧光素酶报告基因、凝胶阻滞、免疫共沉淀、位点突变、RNA干涉及基因过表达等试验技术探讨FOXM1基因通过转录水平激活survivin基因的表达参与结肠肝转移表型形成的分子机制，从而为临床个体化治疗结肠癌肝转移提供准确的分子靶标。

The liver is the most common site of distant metastasis from colorectal cancer(CRC), and this process may be associated with expression of metastatic related proteins and their regulation. FOXM1(Forkhead box protein M1)belongs to a large family of forkhead box(Fox)transcription factors. Previous studies show that the status of FOXM1 expression in CRC tissues is significantly correlated with clinical stage, lymph node metatasis and prognosis of patients with CRC, but the roles of FOXM1 in liver matastasis of CRC and the mechanisms of its transcriptional regulation are still unclear. On the basis of past successful selection of transcription factor microarray asscociated with liver metastsis of CRC, the aim of this study is to investigate the correlation of FOXM1 expression with liver metastasis of CRC at both celluar level and animal level. By luciferase reporter, gel retardation, co-immunoprecipitation, RNA interference and gene-overexpression assays, we next further explore the molecular mechanisms of FOXM1 promoting the liver metastasis of CRC by ativation of survivin at the transcriptional level, which will provide a novel molecular target for the treatment of human CRC.