RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer

Abstract Breast cancer is a complex heterogeneous disease. Common hallmark features of cancer can be found. Their origin may be traced back to their intricate relationships governing regulatory programs during the development of this disease. To unveil distinctive features of the transcriptional reg...

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Autores principales:	Jesús Espinal-Enríquez, Cristóbal Fresno, Guillermo Anda-Jáuregui, Enrique Hernández-Lemus
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/44770fc9d32c4704807cdbc05ae6c593
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spelling	oai:doaj.org-article:44770fc9d32c4704807cdbc05ae6c5932021-12-02T15:06:15ZRNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer10.1038/s41598-017-01314-12045-2322https://doaj.org/article/44770fc9d32c4704807cdbc05ae6c5932017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01314-1https://doaj.org/toc/2045-2322Abstract Breast cancer is a complex heterogeneous disease. Common hallmark features of cancer can be found. Their origin may be traced back to their intricate relationships governing regulatory programs during the development of this disease. To unveil distinctive features of the transcriptional regulation program in breast cancer, a pipeline for RNA-seq analysis in 780 breast cancer and 101 healthy breast samples, at gene expression and network level, was implemented. Inter-chromosomal relationships between genes resulted strikingly scarce in a cancer network, in comparison to its healthy counterpart. We suggest that inter-chromosomal regulation loss may be a novel feature in breast cancer. Additional evidence was obtained by independent validation in microarray and Hi-C data as well as supplementary computational analyses. Functional analysis showed upregulation in processes related to cell cycle and division; while migration, adhesion and cell-to-cell communication, were downregulated. Both the BRCA1 DNA repairing signalling and the Estrogen-mediated G1/S phase entry pathways were found upregulated. In addition, a synergistic underexpression of the γ-protocadherin complex, located at Chr5q31 is also shown. This region has previously been reported to be hypermethylated in breast cancer. These findings altogether provide further evidence for the central role of transcriptional regulatory programs in shaping malignant phenotypes.Jesús Espinal-EnríquezCristóbal FresnoGuillermo Anda-JáureguiEnrique Hernández-LemusNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-19 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jesús Espinal-Enríquez Cristóbal Fresno Guillermo Anda-Jáuregui Enrique Hernández-Lemus RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer
description	Abstract Breast cancer is a complex heterogeneous disease. Common hallmark features of cancer can be found. Their origin may be traced back to their intricate relationships governing regulatory programs during the development of this disease. To unveil distinctive features of the transcriptional regulation program in breast cancer, a pipeline for RNA-seq analysis in 780 breast cancer and 101 healthy breast samples, at gene expression and network level, was implemented. Inter-chromosomal relationships between genes resulted strikingly scarce in a cancer network, in comparison to its healthy counterpart. We suggest that inter-chromosomal regulation loss may be a novel feature in breast cancer. Additional evidence was obtained by independent validation in microarray and Hi-C data as well as supplementary computational analyses. Functional analysis showed upregulation in processes related to cell cycle and division; while migration, adhesion and cell-to-cell communication, were downregulated. Both the BRCA1 DNA repairing signalling and the Estrogen-mediated G1/S phase entry pathways were found upregulated. In addition, a synergistic underexpression of the γ-protocadherin complex, located at Chr5q31 is also shown. This region has previously been reported to be hypermethylated in breast cancer. These findings altogether provide further evidence for the central role of transcriptional regulatory programs in shaping malignant phenotypes.
format	article
author	Jesús Espinal-Enríquez Cristóbal Fresno Guillermo Anda-Jáuregui Enrique Hernández-Lemus
author_facet	Jesús Espinal-Enríquez Cristóbal Fresno Guillermo Anda-Jáuregui Enrique Hernández-Lemus
author_sort	Jesús Espinal-Enríquez
title	RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer
title_short	RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer
title_full	RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer
title_fullStr	RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer
title_full_unstemmed	RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer
title_sort	rna-seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/44770fc9d32c4704807cdbc05ae6c593
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RNA-Seq based genome-wide analysis reveals loss of inter-chromosomal regulation in breast cancer

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