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Title: Large differences in global transcriptional regulatory programs of normal and tumor colon cells
Author: Cordero Romera, David
Solé Acha, Xavier
Crous Bou, Marta
Sanz Pamplona, Rebeca
Paré, Laia
Guinó, Elisabet
Olivares, David
Berenguer, Antoni
Santos, Cristina
Salazar Soler, Ramón
Biondo, Sebastián
Moreno Aguado, Víctor
Keywords: Càncer colorectal
Expressió gènica
Transcripció genètica
Factors de transcripció
Cèl·lules canceroses
Colorectal cancer
Gene expression
Genetic transcription
Transcription factors
Cancer cells
Issue Date: 24-Sep-2014
Publisher: BioMed Central
Abstract: Background: Dysregulation of transcriptional programs leads to cell malfunctioning and can have an impact in cancer development. Our study aims to characterize global differences between transcriptional regulatory programs of normal and tumor cells of the colon. Methods: Affymetrix Human Genome U219 expression arrays were used to assess gene expression in 100 samples of colon tumor and their paired adjacent normal mucosa. Transcriptional networks were reconstructed using ARACNe algorithm using 1,000 bootstrap replicates consolidated into a consensus network. Networks were compared regarding topology parameters and identified well-connected clusters. Functional enrichment was performed with SIGORA method. ENCODE ChIP-Seq data curated in the hmChIP database was used for in silico validation of the most prominent transcription factors. Results: The normal network contained 1,177 transcription factors, 5,466 target genes and 61,226 transcriptional interactions. A large loss of transcriptional interactions in the tumor network was observed (11,585; 81% reduction), which also contained fewer transcription factors (621; 47% reduction) and target genes (2,190; 60% reduction) than the normal network. Gene silencing was not a main determinant of this loss of regulatory activity, since the average gene expression was essentially conserved. Also, 91 transcription factors increased their connectivity in the tumor network. These genes revealed a tumor-specific emergent transcriptional regulatory program with significant functional enrichment related to colorectal cancer pathway. In addition, the analysis of clusters again identified subnetworks in the tumors enriched for cancer related pathways (immune response, Wnt signaling, DNA replication, cell adherence, apoptosis, DNA repair, among others). Also multiple metabolism pathways show differential clustering between the tumor and normal network. Conclusions: These findings will allow a better understanding of the transcriptional regulatory programs altered in colon cancer and could be an invaluable methodology to identify potential hubs with a relevant role in the field of cancer diagnosis, prognosis and therapy.
Note: Reproducció del document publicat a:
It is part of: BMC Cancer, 2014, vol. 14, p. 708
Related resource:
ISSN: 1471-2407
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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