Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer

Cebola, Inês; Custodio Rojo, Joaquín; Muñoz, Mar; Díez-Villanueva, Anna; Paré Brunet, Laia; Prieto, Patricia; Aussó, Susanna|||0000-0002-6981-0752; Coll-Mulet, Llorenç; Boscá, Lisardo|||0000-0002-0253-5469; Moreno Aguado, Victor Raul|||0000-0002-2818-5487; Peinado Morales, Miguel Á.

Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer

Background: Misregulation of the PTGS (prostaglandin endoperoxide synthase, also known as cyclooxygenase or COX) pathway may lead to the accumulation of pro-inflammatory signals, which constitutes a hallmark of cancer. To get insight into the role of this signaling pathway in colorectal cancer (CRC)...

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Autores:	Cebola, Inês, Custodio Rojo, Joaquín, Muñoz, Mar, Díez-Villanueva, Anna, Paré Brunet, Laia, Prieto, Patricia, Aussó, Susanna\|\|\|0000-0002-6981-0752, Coll-Mulet, Llorenç, Boscá, Lisardo\|\|\|0000-0002-0253-5469, Moreno Aguado, Victor Raul\|\|\|0000-0002-2818-5487, Peinado Morales, Miguel Á.
Tipo de documento:	artigo
Data de publicação:	2015
País:	España
Recursos:	Universitat Autònoma de Barcelona
Repositório:	Dipòsit Digital de Documents de la UAB
Idioma:	inglês
OAI Identifier:	oai:ddd.uab.cat:157794
Acesso em linha:	https://ddd.uab.cat/record/157794 https://dx.doi.org/urn:doi:10.1186/s13148-015-0110-4
Access Level:	Acceso aberto
Palavra-chave:	DNA methylation Gene expression COX pathway Prostanoids Inflammation Prostaglandins

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spelling	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancerCebola, InêsCustodio Rojo, JoaquínMuñoz, MarDíez-Villanueva, AnnaParé Brunet, LaiaPrieto, PatriciaAussó, Susanna\|\|\|0000-0002-6981-0752Coll-Mulet, LlorençBoscá, Lisardo\|\|\|0000-0002-0253-5469Moreno Aguado, Victor Raul\|\|\|0000-0002-2818-5487Peinado Morales, Miguel Á.DNA methylationGene expressionCOX pathwayProstanoidsInflammationProstaglandinsBackground: Misregulation of the PTGS (prostaglandin endoperoxide synthase, also known as cyclooxygenase or COX) pathway may lead to the accumulation of pro-inflammatory signals, which constitutes a hallmark of cancer. To get insight into the role of this signaling pathway in colorectal cancer (CRC), we have characterized the transcriptional and epigenetic landscapes of the PTGS pathway genes in normal and cancer cells. Results: Data from four independent series of CRC patients (502 tumors including adenomas and carcinomas and 222 adjacent normal tissues) and two series of colon mucosae from 69 healthy donors have been included in the study. Gene expression was analyzed by real-time PCR and Affymetrix U219 arrays. DNA methylation was analyzed by bisulfite sequencing, dissociation curves, and HumanMethylation450K arrays. Most CRC patients show selective transcriptional deregulation of the enzymes involved in the synthesis of prostanoids and their receptors in both tumor and its adjacent mucosa. DNA methylation alterations exclusively affect the tumor tissue (both adenomas and carcinomas), redirecting the transcriptional deregulation to activation of prostaglandin E2 (PGE2) function and blockade of other biologically active prostaglandins. In particular, PTGIS, PTGER3, PTGFR, and AKR1B1 were hypermethylated in more than 40 % of all analyzed tumors. Conclusions: The transcriptional and epigenetic profiling of the PTGS pathway provides important clues on the biology of the tumor and its microenvironment. This analysis renders candidate markers with potential clinical applicability in risk assessment and early diagnosis and for the design of new therapeutic strategies. 22015-01-0120152015-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/157794https://dx.doi.org/urn:doi:10.1186/s13148-015-0110-4reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2011/23638Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014/52492Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PTC2011/1091Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI11/01439Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CIBERESP/CB06/02/2005Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-647open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1577942026-06-06T12:50:31Z
dc.title.none.fl_str_mv	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
title	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
spellingShingle	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer Cebola, Inês DNA methylation Gene expression COX pathway Prostanoids Inflammation Prostaglandins
title_short	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
title_full	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
title_fullStr	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
title_full_unstemmed	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
title_sort	Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
dc.creator.none.fl_str_mv	Cebola, Inês Custodio Rojo, Joaquín Muñoz, Mar Díez-Villanueva, Anna Paré Brunet, Laia Prieto, Patricia Aussó, Susanna\|\|\|0000-0002-6981-0752 Coll-Mulet, Llorenç Boscá, Lisardo\|\|\|0000-0002-0253-5469 Moreno Aguado, Victor Raul\|\|\|0000-0002-2818-5487 Peinado Morales, Miguel Á.
author	Cebola, Inês
author_facet	Cebola, Inês Custodio Rojo, Joaquín Muñoz, Mar Díez-Villanueva, Anna Paré Brunet, Laia Prieto, Patricia Aussó, Susanna\|\|\|0000-0002-6981-0752 Coll-Mulet, Llorenç Boscá, Lisardo\|\|\|0000-0002-0253-5469 Moreno Aguado, Victor Raul\|\|\|0000-0002-2818-5487 Peinado Morales, Miguel Á.
author_role	author
author2	Custodio Rojo, Joaquín Muñoz, Mar Díez-Villanueva, Anna Paré Brunet, Laia Prieto, Patricia Aussó, Susanna\|\|\|0000-0002-6981-0752 Coll-Mulet, Llorenç Boscá, Lisardo\|\|\|0000-0002-0253-5469 Moreno Aguado, Victor Raul\|\|\|0000-0002-2818-5487 Peinado Morales, Miguel Á.
author2_role	author author author author author author author author author author
dc.subject.none.fl_str_mv	DNA methylation Gene expression COX pathway Prostanoids Inflammation Prostaglandins
topic	DNA methylation Gene expression COX pathway Prostanoids Inflammation Prostaglandins
description	Background: Misregulation of the PTGS (prostaglandin endoperoxide synthase, also known as cyclooxygenase or COX) pathway may lead to the accumulation of pro-inflammatory signals, which constitutes a hallmark of cancer. To get insight into the role of this signaling pathway in colorectal cancer (CRC), we have characterized the transcriptional and epigenetic landscapes of the PTGS pathway genes in normal and cancer cells. Results: Data from four independent series of CRC patients (502 tumors including adenomas and carcinomas and 222 adjacent normal tissues) and two series of colon mucosae from 69 healthy donors have been included in the study. Gene expression was analyzed by real-time PCR and Affymetrix U219 arrays. DNA methylation was analyzed by bisulfite sequencing, dissociation curves, and HumanMethylation450K arrays. Most CRC patients show selective transcriptional deregulation of the enzymes involved in the synthesis of prostanoids and their receptors in both tumor and its adjacent mucosa. DNA methylation alterations exclusively affect the tumor tissue (both adenomas and carcinomas), redirecting the transcriptional deregulation to activation of prostaglandin E2 (PGE2) function and blockade of other biologically active prostaglandins. In particular, PTGIS, PTGER3, PTGFR, and AKR1B1 were hypermethylated in more than 40 % of all analyzed tumors. Conclusions: The transcriptional and epigenetic profiling of the PTGS pathway provides important clues on the biology of the tumor and its microenvironment. This analysis renders candidate markers with potential clinical applicability in risk assessment and early diagnosis and for the design of new therapeutic strategies.
publishDate	2015
dc.date.none.fl_str_mv	2 2015-01-01 2015 2015-01-01
dc.type.none.fl_str_mv	Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://ddd.uab.cat/record/157794 https://dx.doi.org/urn:doi:10.1186/s13148-015-0110-4
url	https://ddd.uab.cat/record/157794 https://dx.doi.org/urn:doi:10.1186/s13148-015-0110-4
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2011/23638 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014/52492 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PTC2011/1091 Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI11/01439 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CIBERESP/CB06/02/2005 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-647
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/3.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona
instname_str	Universitat Autònoma de Barcelona
reponame_str	Dipòsit Digital de Documents de la UAB
collection	Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer

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