Web of Science: 14 citations, Scopus: 14 citations, Google Scholar: citations,
Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer
Cebola, Inês (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Custodio Rojo, Joaquín (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Muñoz, Mar (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Díez-Villanueva, Anna (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Paré, Laia (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Prieto, Patricia (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Aussó, Susanna (Institut Català d'Oncologia)
Coll-Mulet, Llorenç (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Boscá, Lisardo (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Moreno Aguado, Víctor (Institut Català d'Oncologia)
Peinado Morales, Miguel Á. (Miguel Ángel) (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)

Date: 2015
Abstract: 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.
Note: Número d'acord de subvenció MINECO/SAF2011/23638
Note: Número d'acord de subvenció MINECO/SAF2014/52492
Note: Número d'acord de subvenció SFRH/BD/28464/2006
Note: Número d'acord de subvenció MINECO/PTC2011/1091
Note: Número d'acord de subvenció ISCIII/PI11/01439
Note: Número d'acord de subvenció CIBERESP/CB06/02/2005
Note: Número d'acord de subvenció AGAUR/2014/SGR-647
Rights: Aquest 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. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: DNA methylation ; Gene expression ; COX pathway ; Prostanoids ; Inflammation ; Prostaglandins
Published in: Clinical epigenetics, Vol. 7 Núm. 7 (July 2015) , ISSN 1868-7075

DOI: 10.1186/s13148-015-0110-4
PMID: 26207152


11 p, 2.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2016-06-09, last modified 2019-02-06



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