Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.

The relationship between peroxisome proliferator-activated receptor γ (PPARG) expression and epigenetic changes occurring in colorectal-cancer pathogenesis is largely unknown. We investigated whether PPARG is epigenetically regulated in colorectal cancer (CRC) progression. PPARG expression was asses...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Massimo Pancione, Lina Sabatino, Alessandra Fucci, Vincenzo Carafa, Angela Nebbioso, Nicola Forte, Antonio Febbraro, Domenico Parente, Concetta Ambrosino, Nicola Normanno, Lucia Altucci, Vittorio Colantuoni
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5eb28233d0a44bc59483ddea5d682d84
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5eb28233d0a44bc59483ddea5d682d84
record_format	dspace
spelling	oai:doaj.org-article:5eb28233d0a44bc59483ddea5d682d842021-11-18T07:02:06ZEpigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.1932-620310.1371/journal.pone.0014229https://doaj.org/article/5eb28233d0a44bc59483ddea5d682d842010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21151932/?tool=EBIhttps://doaj.org/toc/1932-6203The relationship between peroxisome proliferator-activated receptor γ (PPARG) expression and epigenetic changes occurring in colorectal-cancer pathogenesis is largely unknown. We investigated whether PPARG is epigenetically regulated in colorectal cancer (CRC) progression. PPARG expression was assessed in CRC tissues and paired normal mucosa by western blot and immunohistochemistry and related to patients' clinicopathological parameters and survival. PPARG promoter methylation was analyzed by methylation-specific-PCR and bisulphite sequencing. PPARG expression and promoter methylation were similarly examined also in CRC derived cell lines. Chromatin immunoprecipitation in basal conditions and after epigenetic treatment was performed along with knocking-down experiments of putative regulatory factors. Gene expression was monitored by immunoblotting and functional assays of cell proliferation and invasiveness. Methylation on a specific region of the promoter is strongly correlated with PPARG lack of expression in 30% of primary CRCs and with patients' poor prognosis. Remarkably, the same methylation pattern is found in PPARG-negative CRC cell lines. Epigenetic treatment with 5'-aza-2'-deoxycytidine can revert this condition and, in combination with trichostatin A, dramatically re-activates gene transcription and receptor activity. Transcriptional silencing is due to the recruitment of MeCP2, HDAC1 and EZH2 that impart repressive chromatin signatures determining an increased cell proliferative and invasive potential, features that can experimentally be reverted. Our findings provide a novel mechanistic insight into epigenetic silencing of PPARG in CRC that may be relevant as a prognostic marker of tumor progression.Massimo PancioneLina SabatinoAlessandra FucciVincenzo CarafaAngela NebbiosoNicola ForteAntonio FebbraroDomenico ParenteConcetta AmbrosinoNicola NormannoLucia AltucciVittorio ColantuoniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e14229 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Massimo Pancione Lina Sabatino Alessandra Fucci Vincenzo Carafa Angela Nebbioso Nicola Forte Antonio Febbraro Domenico Parente Concetta Ambrosino Nicola Normanno Lucia Altucci Vittorio Colantuoni Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
description	The relationship between peroxisome proliferator-activated receptor γ (PPARG) expression and epigenetic changes occurring in colorectal-cancer pathogenesis is largely unknown. We investigated whether PPARG is epigenetically regulated in colorectal cancer (CRC) progression. PPARG expression was assessed in CRC tissues and paired normal mucosa by western blot and immunohistochemistry and related to patients' clinicopathological parameters and survival. PPARG promoter methylation was analyzed by methylation-specific-PCR and bisulphite sequencing. PPARG expression and promoter methylation were similarly examined also in CRC derived cell lines. Chromatin immunoprecipitation in basal conditions and after epigenetic treatment was performed along with knocking-down experiments of putative regulatory factors. Gene expression was monitored by immunoblotting and functional assays of cell proliferation and invasiveness. Methylation on a specific region of the promoter is strongly correlated with PPARG lack of expression in 30% of primary CRCs and with patients' poor prognosis. Remarkably, the same methylation pattern is found in PPARG-negative CRC cell lines. Epigenetic treatment with 5'-aza-2'-deoxycytidine can revert this condition and, in combination with trichostatin A, dramatically re-activates gene transcription and receptor activity. Transcriptional silencing is due to the recruitment of MeCP2, HDAC1 and EZH2 that impart repressive chromatin signatures determining an increased cell proliferative and invasive potential, features that can experimentally be reverted. Our findings provide a novel mechanistic insight into epigenetic silencing of PPARG in CRC that may be relevant as a prognostic marker of tumor progression.
format	article
author	Massimo Pancione Lina Sabatino Alessandra Fucci Vincenzo Carafa Angela Nebbioso Nicola Forte Antonio Febbraro Domenico Parente Concetta Ambrosino Nicola Normanno Lucia Altucci Vittorio Colantuoni
author_facet	Massimo Pancione Lina Sabatino Alessandra Fucci Vincenzo Carafa Angela Nebbioso Nicola Forte Antonio Febbraro Domenico Parente Concetta Ambrosino Nicola Normanno Lucia Altucci Vittorio Colantuoni
author_sort	Massimo Pancione
title	Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
title_short	Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
title_full	Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
title_fullStr	Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
title_full_unstemmed	Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
title_sort	epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/5eb28233d0a44bc59483ddea5d682d84
work_keys_str_mv	AT massimopancione epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT linasabatino epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT alessandrafucci epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT vincenzocarafa epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT angelanebbioso epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT nicolaforte epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT antoniofebbraro epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT domenicoparente epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT concettaambrosino epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT nicolanormanno epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT luciaaltucci epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome AT vittoriocolantuoni epigeneticsilencingofperoxisomeproliferatoractivatedreceptorgisabiomarkerforcolorectalcancerprogressionandadversepatientsoutcome
_version_	1718424042700013568

Epigenetic silencing of peroxisome proliferator-activated receptor γ is a biomarker for colorectal cancer progression and adverse patients' outcome.

Ejemplares similares