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, CSF1R, MMP9, PDGFRB, FIGF and IL6, regulates cell migration. Therefore, CREB5 might accelerate the metastasis of colorectal cancer by regulating these five key genes.
Lu Qi, Yanqing Ding
. Involvement of the CREB5 regulatory network in colorectal cancer metastasis[J]. Hereditas(Beijing), 2014
, 36(7)
: 679
-684
.
DOI: 10.3724/SP.J.1005.2014.0679
[1] A, Kuehn H, Gould J, Tamayo P, Mesirov JP. GSEA-P: a desktop application for gene set enrichment analysis. Bioinformatics , 2007, 23(23): 3251-3253.
[2] 丁彦青. 大肠癌转移相关基因表达调控的生物信息学分析. 基因组学与应用生物学, 2013, (1): 83-90.
[3] VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA , 2001, 98(9): 5116-5121.
[5] L, Touzet H, Varre JS. TFM-Explorer: mining cis-regulatory regions in genomes. Nucleic Acids Res , 2010, 38(S2): W286-W292.
[6] L, Ding YQ. Screening and regulatory network analysis of survival-related genes of patients with colorectal cancer. Sci China Life Sci , 2014, 57(5): 526-531.
[7] 丁彦青. 大肠癌患者生存相关基因的筛选与网络调控分析. 中国科学(生命科学), 2014, 44(5): 481-487.
[8] YL, Maekawa T, Nomura N, Nakata T, Ishii S. Regulation of trans-activating capacity of CRE-BPa by phorbol ester tumor promoter TPA. Oncogene , 1993, 8(10): 2749-2758.
[9] N, Zu YL, Maekawa T, Tabata S, Akiyama T, Ishii S. Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. J Biol Chem , 1993, 268(6): 4259-4266.
[10] JP. The NCBI. Publicly available tools and resources on the Web. Methods Mol Biol , 2000, 132: 301-312.
[11] T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C, Kim IF, Soboleva A, Tomashevsky M, Edgar R. NCBI GEO: mining tens of millions of expression profiles database and tools update. Nucleic Acids Res , 2007, 35(S1): D760-D765.
[12] M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res , 2000, 28(1): 27-30.
[13] J, Angel P, Schorpp-Kistner M. AP-1 subunits: quarrel and harmony among siblings. J Cell Sci , 2004, 117(Pt 25): 5965-5973.
[14] S, Ray D, Warde-Farley D, Grouios C, Morris Q. GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function. G e nome Biol , 2008, 9(Suppl.1): S4.
[15] B, Kirov S, Snoddy J. WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res , 2005, 33(S2): W741-W748.
