CREB5在大肠癌转移中的调控机制  

Involvement of the CREB5 regulatory network in colorectal cancer metastasis

作　　者：齐鲁[1] 丁彦青[1,2] 

机构地区：[1]南方医科大学基础医学院病理学系,广州510515 [2]南方医科大学南方医院病理科,广州510515

出　　处：《遗传》2014年第7期679-684,共6页Hereditas（Beijing)

基　　金：国家自然科学基金联合基金项目(编号:U1201226)和国家自然科学基金项目(编号:30670967)资助

摘　　要：大肠癌转移过程中所涉及的细胞信号调控网络非常复杂,寻找调控网络中的关键调控点对阐明大肠癌转移机制以及寻找药物治疗靶点均具有重要意义。研究表明,CREB5(cAMP responsive element binding protein 5)可能为大肠癌转移相关信号调控网络中的关键基因。文章基于大肠癌表达谱数据,根据CREB5基因表达值的大小对大肠癌的相关分子事件进行了富集分析,发现这些分子事件与肿瘤转移密切相关。根据CREB5能够和c-Jun结合成为异二聚体的特点,联合分析转录因子AP-1结合位点的富集情况,筛选出在CREB5基因高表达组中表达上调、具有AP-1结合位点、且属于癌症通路的基因16个,这些基因所构成的分子网络与细胞迁移功能类相关度最高。细胞迁移功能类主要由5个基因——CSF1R、MMP9、PDGFRB、FIGF和IL6所构成,因此CREB5可能是通过调控这5个关键基因进而促进大肠癌的转移。The signal regulatory network involved in colorectal cancer metastasis is complicated and thus the search for key control steps in the network is of great significance for unraveling colorectal cancer metastasis mechanism and finding drug-target site. Previous studies suggested that CREB5 （cAMP responsive element binding protein 5） might play key role in the metastatic signal network of colorectal cancer. Through colorectal cancer expression profile and enriching analysis of the effect of CREB5 gene expression levels on colorectal cancer molecular events, we found that these molecular events are correlated with tumor metastasis. Based on the feature that CREB5 could combine with c-Jun to form heterodimer, together with enriched binding sites for transcription factor AP-1, we identified 16 genes which were up-regulated in the CREB5 high-expression group, contained AP-1 binding sites, and participated in cancer pathway. The molecular network involving these 16 genes, in particular, CSFIR, MMP9, PDGFRB, FIGF and IL6, regulates cell migration. Therefore, CREB5 might accelerate the metastasis of colorectal cancer by regulating these five key genes.

关 键 词：CREB5 大肠癌 转移 生物信息学 

分 类 号：R735.34[医药卫生—肿瘤]