Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/127456
Title: Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer.
Author: Cebola, Inés
Custodio, Joaquin
Muñoz, Mar
Díez Villanueva, Anna
Paré, Laia
Prieto, Patricia
Aussó, Susanna
Coll Mulet, Llorenç
Boscá, Lisardo
Moreno Aguado, Víctor
Peinado, Miguel A.
Keywords: Prostaglandines
Inflamació
Epigenètica
Expressió gènica
Càncer colorectal
Prostaglandins
Inflammation
Epigenetics
Gene expression
Colorectal cancer
Issue Date: 24-Jul-2015
Publisher: BioMed Central
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: Reproducció del document publicat a: https://doi.org/10.1186/s13148-015-0110-4
It is part of: Clinical Epigenetics, 2015, vol. 7, num. 74
URI: http://hdl.handle.net/2445/127456
Related resource: https://doi.org/10.1186/s13148-015-0110-4
ISSN: 1868-7075
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

Files in This Item:
File Description SizeFormat 
660404.pdf2.62 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons