The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.

Metabolic transformations have been reported as involved in neoplasms survival. This suggests a role of metabolic pathways as potential cancer pharmacological targets. Modulating tumor's energy production pathways may become a substantial research area for cancer treatment. The significant role...

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Autores principales:	Karol Baca-López, Miguel Mayorga, Alfredo Hidalgo-Miranda, Nora Gutiérrez-Nájera, Enrique Hernández-Lemus
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85ab2ec0dd2243ed9cc899d3a4752554
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spelling	oai:doaj.org-article:85ab2ec0dd2243ed9cc899d3a47525542021-11-18T07:07:36ZThe role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.1932-620310.1371/journal.pone.0042678https://doaj.org/article/85ab2ec0dd2243ed9cc899d3a47525542012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952604/?tool=EBIhttps://doaj.org/toc/1932-6203Metabolic transformations have been reported as involved in neoplasms survival. This suggests a role of metabolic pathways as potential cancer pharmacological targets. Modulating tumor's energy production pathways may become a substantial research area for cancer treatment. The significant role of metabolic deregulation as inducing transcriptional instabilities and consequently whole-system failure, is thus of foremost importance. By using a data integration approach that combines experimental evidence for high-throughput genome wide gene expression, a non-equilibrium thermodynamics analysis, nonlinear correlation networks as well as database mining, we were able to outline the role that transcription factors MEF2C and MNDA may have as main master regulators in primary breast cancer phenomenology, as well as the possible interrelationship between malignancy and metabolic dysfunction. The present findings are supported by the analysis of 1191 whole genome gene expression experiments, as well as probabilistic inference of gene regulatory networks, and non-equilibrium thermodynamics of such data. Other evidence sources include pathway enrichment and gene set enrichment analyses, as well as motif comparison with a comprehensive gene regulatory network (of homologue genes) in Arabidopsis thaliana. Our key finding is that the non-equilibrium free energies provide a realistic description of transcription factor activation that when supplemented with gene regulatory networks made us able to find deregulated pathways. These analyses also suggest a novel potential role of transcription factor energetics at the onset of primary tumor development. Results are important in the molecular systems biology of cancer field, since deregulation and coupling mechanisms between metabolic activity and transcriptional regulation can be better understood by taking into account the way that master regulators respond to physicochemical constraints imposed by different phenotypic conditions.Karol Baca-LópezMiguel MayorgaAlfredo Hidalgo-MirandaNora Gutiérrez-NájeraEnrique Hernández-LemusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42678 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karol Baca-López Miguel Mayorga Alfredo Hidalgo-Miranda Nora Gutiérrez-Nájera Enrique Hernández-Lemus The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.
description	Metabolic transformations have been reported as involved in neoplasms survival. This suggests a role of metabolic pathways as potential cancer pharmacological targets. Modulating tumor's energy production pathways may become a substantial research area for cancer treatment. The significant role of metabolic deregulation as inducing transcriptional instabilities and consequently whole-system failure, is thus of foremost importance. By using a data integration approach that combines experimental evidence for high-throughput genome wide gene expression, a non-equilibrium thermodynamics analysis, nonlinear correlation networks as well as database mining, we were able to outline the role that transcription factors MEF2C and MNDA may have as main master regulators in primary breast cancer phenomenology, as well as the possible interrelationship between malignancy and metabolic dysfunction. The present findings are supported by the analysis of 1191 whole genome gene expression experiments, as well as probabilistic inference of gene regulatory networks, and non-equilibrium thermodynamics of such data. Other evidence sources include pathway enrichment and gene set enrichment analyses, as well as motif comparison with a comprehensive gene regulatory network (of homologue genes) in Arabidopsis thaliana. Our key finding is that the non-equilibrium free energies provide a realistic description of transcription factor activation that when supplemented with gene regulatory networks made us able to find deregulated pathways. These analyses also suggest a novel potential role of transcription factor energetics at the onset of primary tumor development. Results are important in the molecular systems biology of cancer field, since deregulation and coupling mechanisms between metabolic activity and transcriptional regulation can be better understood by taking into account the way that master regulators respond to physicochemical constraints imposed by different phenotypic conditions.
format	article
author	Karol Baca-López Miguel Mayorga Alfredo Hidalgo-Miranda Nora Gutiérrez-Nájera Enrique Hernández-Lemus
author_facet	Karol Baca-López Miguel Mayorga Alfredo Hidalgo-Miranda Nora Gutiérrez-Nájera Enrique Hernández-Lemus
author_sort	Karol Baca-López
title	The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.
title_short	The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.
title_full	The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.
title_fullStr	The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.
title_full_unstemmed	The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.
title_sort	role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/85ab2ec0dd2243ed9cc899d3a4752554
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The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas.

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