HOXB7调控NKX3-1促进大肠癌转移机制分析

HOXB7 promotes colorectal cancer metastasis through targeting NKX3-1

目的分析HOXB7基因的过表达表达谱数据,探索HOXB7基因在大肠癌发生和转移过程中可能参与的分子机制。方法通过对HOXB7基因过表达的大肠癌细胞株对比空载对照组中表达具有差异的基因,进行转录因子结合位点富集分析,富集的转录因子结合位点与差异基因取交集,得到表达具有差异的转录因子结合位点,对具有此转录因子结合位点的差异表达基因进行共表达分析,明确这些基因可能具有的共表达特性,并对这些共表达基因对应的蛋白进行蛋白相互作用网络调控分析,明确这些基因可能参与的细胞信号通路。结果转录因子NKX3-1结合位点在HOXB7过表达的上调差异基因中的转录调控区域富集程度较高,且其本身为上调的差异基因,推测其可能在部分上调基因中具有调控作用。而NKX3-1基因与具有其转录因子结合位点的14个基因存在着共表达关系,且这14个基因所主导的细胞信号子网络主要参与肿瘤相关通路、Wnt信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、细胞间连接、细胞与细胞外基质连接等与肿瘤发生及转移密切相关的信号通路。结论 HOXB7基因可能通过调控NKX3-1基因促进大肠癌的发生和转移。

Objective To investigate the molecular mechanism underlying the occurrence and metastasis of colorectal cancer by analyzing the HOXB7 gene over-expression profile. Methods The enriched transcription factor binding site （TFBS） was analyzed by comparing the different genes of HOXB7 over- expressed colon cancer cell strain and blank control group. Intersection genes of enriched TFBS and differential genes were obtained to get differential TFBS and co-expression genes of which were analyzed to clarify the co-expression features. The interactive regulatory network of correlated proteins was analyzed to determine the potential cell signal pathways in which these genes participated. Results It was assumed that the transcription factor NKX3-1 might regulate some up-regulated genes because its combining site was highly enriched in transcript region of HOXB7 over-expressed genes and it was an up- regulated differential gene. The NKX3-1 gene had the co-expression relationship with other 14 genes within TFBS and the molecular signal network controlled by which mainly participated in signal pathways of tumor related, Writ, MAPK, intercellular connection, and extracellular matrix connection that were closely related to tumor occurrence and metastasis. Conclusion HOXB7 gene might accelerate the occurrence and metastasis of colon cancer by regulating the NKX3-1 gene.