生物节律基因CLOCK与大肠癌预后的相关性及分子机制研究

项目名称： 生物节律基因CLOCK与大肠癌预后的相关性及分子机制研究

项目编号： No.81201583

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 周峰

作者单位： 徐州医学院

项目金额： 23万元

中文摘要： 我国大肠癌防治形势日益严峻，临床用于评估大肠癌预后的血清学指标又极为匮乏，亟待寻找新型分子标志物。目前大量研究已证实生物节律基因CLOCK可通过调控c-Myc、P21、P53等钟控基因的表达，在多种疾病包括肿瘤的发生及进展中发挥重要作用，但在大肠癌领域的研究较少。2012年项目申请者在《Cancer》杂志上首次报道了CLOCK基因rs3749474及rs1801260位点与大肠癌患者预后显著相关。本项目拟在此基础上进一步探讨CLOCK基因蛋白表达水平与SNP基因型及大肠癌患者预后之间的相关性，利用siRNA干涉技术下调大肠癌细胞中CLOCK基因的表达，检测细胞生物学功能改变及c-Myc、P21、P53等钟控基因的表达变化，并通过全基因组表达芯片构建CLOCK基因的分子调控网络，深入探讨CLOCK基因影响大肠癌患者预后的分子作用机制，为大肠癌新型分子标志物的研究提供实验证据及理论支持。

中文关键词： CLOCK；生物节律；大肠癌；预后；

英文摘要： The preventive and therapeutic situation on colorectal cancer in our country is becoming increasingly serious. However, the serum tumor marker for the diagnosis of colorectal cancer is extremely limited. Thus, it is an urgent need to explore more novel tumor markers. Increasing evidences have indicated that CLOCK, a family member of the circadian genes, can control the expression of many so-called clock-controlled genes (CCGs), especially including c-Myc, P21, P53. The CLOCK gene may contribute to the development and progression of many kinds of diseases including cancer, but little work has been focus on its role in colorectal cancer. Two SNPs (rs3749474 and rs1801260) located in the CLOCK gene are significantly associated with colorectal caner overall survival in our earlier studies and the related article has been published in 《Cancer》 in 2012. Based on that, this project will further analysis the association of expression level of CLOCK gene and SNP genotype with prognosis of colorectal cancer patients. We will use siRNA technology to interfere the expression level of the CLOCK gene in colorectal cancer cells, and then its effect on biological activity of tumor cells will be analyzed and the related fold changes of its target gene such as c-Myc, P21, P53 and etc will also be detected. The whole-genome expres

英文关键词： CLOCK；circadian；colorectal；prognosis；