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, Inés, Custodio, Joaquin, Muñoz, Mar, Díez Villanueva, Anna, Paré, Laia, Prieto, Patricia, Aussó, Susanna, Coll Mulet, Llorenç, Boscá, Lisardo, Moreno Aguado, Víctor, Peinado Morales, Miguel Á. (Miguel Ángel)
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/127456
Acceso en línea:https://hdl.handle.net/2445/127456
Access Level:acceso abierto
Palabra clave:Prostaglandines
Inflamació
Epigenètica
Expressió gènica
Càncer colorectal
Prostaglandins
Inflammation
Epigenetics
Gene expression
Colorectal cancer
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spelling Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer.Cebola, InésCustodio, JoaquinMuñoz, MarDíez Villanueva, AnnaParé, LaiaPrieto, PatriciaAussó, SusannaColl Mulet, LlorençBoscá, LisardoMoreno Aguado, VíctorPeinado Morales, Miguel Á. (Miguel Ángel)ProstaglandinesInflamacióEpigenèticaExpressió gènicaCàncer colorectalProstaglandinsInflammationEpigeneticsGene expressionColorectal cancerBACKGROUND: 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.BioMed Central2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/127456Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s13148-015-0110-4Clinical Epigenetics, 2015, vol. 7, num. 74https://doi.org/10.1186/s13148-015-0110-4cc-by (c) Cebola, Inés et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1274562026-05-27T06:46:51Z
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, Inés
Prostaglandines
Inflamació
Epigenètica
Expressió gènica
Càncer colorectal
Prostaglandins
Inflammation
Epigenetics
Gene expression
Colorectal cancer
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, Inés
Custodio, Joaquin
Muñoz, Mar
Díez Villanueva, Anna
Paré, Laia
Prieto, Patricia
Aussó, Susanna
Coll Mulet, Llorenç
Boscá, Lisardo
Moreno Aguado, Víctor
Peinado Morales, Miguel Á. (Miguel Ángel)
author Cebola, Inés
author_facet Cebola, Inés
Custodio, Joaquin
Muñoz, Mar
Díez Villanueva, Anna
Paré, Laia
Prieto, Patricia
Aussó, Susanna
Coll Mulet, Llorenç
Boscá, Lisardo
Moreno Aguado, Víctor
Peinado Morales, Miguel Á. (Miguel Ángel)
author_role author
author2 Custodio, Joaquin
Muñoz, Mar
Díez Villanueva, Anna
Paré, Laia
Prieto, Patricia
Aussó, Susanna
Coll Mulet, Llorenç
Boscá, Lisardo
Moreno Aguado, Víctor
Peinado Morales, Miguel Á. (Miguel Ángel)
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Prostaglandines
Inflamació
Epigenètica
Expressió gènica
Càncer colorectal
Prostaglandins
Inflammation
Epigenetics
Gene expression
Colorectal cancer
topic Prostaglandines
Inflamació
Epigenètica
Expressió gènica
Càncer colorectal
Prostaglandins
Inflammation
Epigenetics
Gene expression
Colorectal cancer
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 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/127456
url https://hdl.handle.net/2445/127456
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s13148-015-0110-4
Clinical Epigenetics, 2015, vol. 7, num. 74
https://doi.org/10.1186/s13148-015-0110-4
dc.rights.none.fl_str_mv cc-by (c) Cebola, Inés et al., 2015
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Cebola, Inés et al., 2015
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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