Jian Tao, Chen Yun
Hepatogastroenterology. 2015 Mar-Apr;62(138):524-8.
BACKGROUND/AIMS: Gastric cancer is one of the most lethal diseases and has caused a global health problem. We aimed to elucidate the major mechanisms involved in the gastric cancer progression.
The expression profile GSE13911 was downloaded from GEO database, composing of 31 normal and 38 tumor samples. The transcription factor (TF)--target gene regulatory network and protein-protein interaction (PPI) network related to gastric cancer were obtained from TRED and TRANSFAC databases. After combining the two networks, we constructed an integrated network.
In total, 5255 DEGs in tumor samples were identified, which were mainly enriched in 12 pathways including cell cycle. The integrated network of TF--target gene--protein interaction included 7 genes related to cell cycle, in which E2F1 was predicted to mediate the expression of MCM4, MCM5 and CDC6 through regulating the expression of its target gene MCM3.
In gastric cancer progression, E2F1 may play vital roles in the involvement of cell cycle pathway through regulating its target gene MCM3, which might interact with MCM4, MCM5 and MCM7. Besides, STAT1 was another potentially critical transcription factor which could regulate multiple target genes.
背景/目的：胃癌是最致命的疾病之一，已成为一个全球性的健康问题。我们旨在阐明参与胃癌进展的主要机制。
从基因表达综合数据库（GEO）下载表达谱GSE13911，其由31个正常样本和38个肿瘤样本组成。从转录因子（TF）反应元件数据库（TRED）和转录因子数据库（TRANSFAC）获得与胃癌相关的转录因子-靶基因调控网络和蛋白质-蛋白质相互作用（PPI）网络。将这两个网络合并后，构建了一个整合网络。
共鉴定出肿瘤样本中的5255个差异表达基因（DEG），主要富集于包括细胞周期在内的12条通路。转录因子-靶基因-蛋白质相互作用的整合网络包含7个与细胞周期相关的基因，其中E2F1被预测通过调节其靶基因MCM3的表达来介导MCM4、MCM5和CDC6的表达。
在胃癌进展过程中，E2F1可能通过调节其靶基因MCM3在细胞周期通路的参与中发挥重要作用，MCM3可能与MCM4、MCM5和MCM7相互作用。此外，信号转导和转录激活因子1（STAT1）是另一个可能关键的转录因子，可调节多个靶基因。
