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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2016, Vol. 10 Issue (2) : 178-182     DOI: 10.1007/s11684-016-0442-2
Bioinformatic exploration of MTA1-regulated gene networks in colon cancer
Chunxiao Li1,Haijuan Wang1,Feng Lin1,Hui Li1,Tao Wen2,Haili Qian1,*(),Qimin Zhan1
1. Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, State Key Laboratory of Molecular Oncology, Beijing 100021, China
2. Beijing Chao-Yang Hospital, Capital Medical University, Medical Research Center, Beijing 100020, China
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Metastasis-associated gene 1 (MTA1) controls a series of biological processes in tumor progression. Tumor progression is a complex process regulated by a gene network. The global cancer gene regulatory network must be analyzed to determine the position of MTA1 in the molecular network and its cooperative genes by further exploring the biological functions of this gene. We used TCGA data sets and GeneCards database to screen MTA1-related genes. GO and KEGG pathway analyses were conducted with DAVID and gene network analysis via STRING and Cytoscape. Results showed that in the development of colon cancer, MTA1 is linked to certain signal pathways, such as Wnt/Notch/nucleotide excision repair pathways. The findings also suggested that MTA1 demonstrates the closest relationship in a coregulation process with the key molecules AKT1, EP300, CREBBP, SMARCA4, RHOA, and CAD. These results lead MTA1 exploration to an in-depth investigation in different directions, such as Wnt, Notch, and DNA repair.

Keywords metastasis-associated gene 1      colon cancer      bioinformatics     
Corresponding Authors: Haili Qian   
Just Accepted Date: 17 March 2016   Online First Date: 06 April 2016    Issue Date: 27 May 2016
URL:     OR
Fig.1  Production of 176 MTA1-related colon cancer genes. Overlapping analysis of the 1103 MTA1-related genes from TCGA and 3625 colon cancer genes from GeneCards.
Fig.2  Gene function annotation and enrichment. (A) GO annotation (biology process) of 176 MTA1-associated colon cancer genes. (B) KEGG pathway of the 176 genes.
Fig.3  Interactive network of MTA1-related genes. A total of 176 MTA1-related colon cancer genes products are analyzed with the interaction via STRING database, thereby forming a complicated multicentric interactive network that includes 134 genes.
Fig.4  Topological features of the interactive network. A total of 134 genes are analyzed with Cytoscape, and the six yellow oval are the top six genes with the highest connectivity values.
1 Toh Y, Pencil SD, Nicolson GL. A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J Biol Chem 1994; 269(37): 22958–22963
pmid: 8083195
2 Nicolson GL, Nawa A, Toh Y, Taniguchi S, Nishimori K, Moustafa A. Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis 2003; 20(1): 19–24
doi: 10.1023/A:1022534217769 pmid: 12650603
3 Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y, Nicolson GL, Sugimachi K. Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer 1997; 74(4): 459–463
doi: 10.1002/(SICI)1097-0215(19970822)74:4<459::AID-IJC18>3.0.CO;2-4 pmid: 9291440
4 Ghanta KS, Li DQ, Eswaran J, Kumar R. Gene profiling of MTA1 identifies novel gene targets and functions. PLoS ONE 2011; 6(2): e17135
doi: 10.1371/journal.pone.0017135 pmid: 21364872
5 Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487(7407): 330–337
doi: 10.1038/nature11252 pmid: 22810696
6 Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013; 6(269): pl1
doi: 10.1126/scisignal.2004088 pmid: 23550210
7 Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012; 2(5): 401–404
doi: 10.1158/2159-8290.CD-12-0095 pmid: 22588877
8 Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D. GeneCards: integrating information about genes, proteins and diseases. Trends Genet 1997; 13(4): 163
doi: 10.1016/S0168-9525(97)01103-7 pmid: 9097728
9 Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37(1): 1–13
doi: 10.1093/nar/gkn923 pmid: 19033363
10 Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4(1): 44–57
doi: 10.1038/nprot.2008.211 pmid: 19131956
11 Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res 2015; 43(Database issue): D447–D452
doi: 10.1093/nar/gku1003 pmid: 25352553
12 Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13(11): 2498–2504
doi: 10.1101/gr.1239303 pmid: 14597658
13 Li DQ, Pakala SB, Nair SS, Eswaran J, Kumar R. Metastasis-associated protein 1/nucleosome remodeling and histone deacetylase complex in cancer. Cancer Res 2012; 72(2): 387–394
doi: 10.1158/0008-5472.CAN-11-2345 pmid: 22253283
14 Liu J, Wang H, Ma F, Xu D, Chang Y, Zhang J, Wang J, Zhao M, Lin C, Huang C, Qian H, Zhan Q. MTA1 regulates higher-order chromatin structure and histone H1-chromatin interaction in-vivo. Mol Oncol 2015; 9(1): 218–235
doi: 10.1016/j.molonc.2014.08.007 pmid: 25205035
15 Dhar S, Kumar A, Li K, Tzivion G, Levenson AS. Resveratrol regulates PTEN/Akt pathway through inhibition of MTA1/HDAC unit of the NuRD complex in prostate cancer. Biochim Biophys Acta 2015; 1853(2): 265–275
doi: 10.1016/j.bbamcr.2014.11.004 pmid: 25447541
16 Ohshiro K, Rayala SK, Wigerup C, Pakala SB, Natha RS, Gururaj AE, Molli PR, Månsson SS, Ramezani A, Hawley RG, Landberg G, Lee NH, Kumar R. Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator. EMBO Rep 2010; 11(9): 691–697
doi: 10.1038/embor.2010.99 pmid: 20651739
17 Nagaraj SR, Shilpa P, Rachaiah K, Salimath BP. Crosstalk between VEGF and MTA1 signaling pathways contribute to aggressiveness of breast carcinoma. Mol Carcinog 2015; 54(5): 333–350
doi: 10.1002/mc.22104 pmid: 24265228
18 Yang YM, Liu H, Li WB. Expression of Mta-1 and VEGF and their correlation in the endometrial cancer. Chin J Cell Mol Immunol (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) 2010; 26(7): 682–684 (in Chinese)
19 Esteller M.Epigenetic changes in cancer. F1000 Biol Rep 2011;3:9<DOI OutputMedium="All">1<?Pub Caret1?>0.3410/B3-9</DOI>
pmid: 21655338
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