Background: Tumor epigenetic defects are of increasing relevance to clinical practice, because they are 'druggable' targets for cancer therapy using chromatin-remodeling agents (CRAs). New evidences highlight the importance of the microenvironment on the epigenome regulation and the need to use culture models able to preserve tissue morphology, to better understand the action of CRAs. Methods & methods: We studied the epigenetic response induced by culturing and CRAs in a preclinical model, preserving ex vivo the original tissue microenvironment and morphology, assessing different epigenetic signatures. Our overall findings suggest that culturing and CRAs cause heterogeneous effects on the genes methylation; CRAs affect the global DNA methylation and can trigger an active DNA demethylation; the culture induces alterations in the histone deacetylase expression. Conclusion: Despite the limited number of cases, these findings can be considered a proof of concept of the possibility to test CRAs epigenetic effects on ex vivo tissues maintained in their native tissue architecture.

Epigenetic effects of chromatin remodeling agents on organotypic cultures / S.M. Sirchia, A. Faversani, D. Rovina, M.V. Russo, L. Paganini, F. Savi, C. Augello, L. Rosso, A. Del Gobbo, S. Tabano, S. Bosari, M. Miozzo. - In: EPIGENOMICS. - ISSN 1750-1911. - 8:3(2016 Mar), pp. 341-358.

Epigenetic effects of chromatin remodeling agents on organotypic cultures

S.M. Sirchia
Primo
;
A. Faversani
Secondo
;
D. Rovina;M.V. Russo;L. Paganini;F. Savi;C. Augello;L. Rosso;A. Del Gobbo;S. Tabano;S. Bosari
Penultimo
;
M. Miozzo
Ultimo
2016-03

Abstract

Background: Tumor epigenetic defects are of increasing relevance to clinical practice, because they are 'druggable' targets for cancer therapy using chromatin-remodeling agents (CRAs). New evidences highlight the importance of the microenvironment on the epigenome regulation and the need to use culture models able to preserve tissue morphology, to better understand the action of CRAs. Methods & methods: We studied the epigenetic response induced by culturing and CRAs in a preclinical model, preserving ex vivo the original tissue microenvironment and morphology, assessing different epigenetic signatures. Our overall findings suggest that culturing and CRAs cause heterogeneous effects on the genes methylation; CRAs affect the global DNA methylation and can trigger an active DNA demethylation; the culture induces alterations in the histone deacetylase expression. Conclusion: Despite the limited number of cases, these findings can be considered a proof of concept of the possibility to test CRAs epigenetic effects on ex vivo tissues maintained in their native tissue architecture.
chromatin remodeling agents; DNA hydroxymethylation; DNA methylation; epigenetics; HDAC; organotypic culture; Genetics; Cancer Research
Settore MED/03 - Genetica Medica
Article (author)
File in questo prodotto:
File Dimensione Formato  
Epigenomics 2016.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 4.86 MB
Formato Adobe PDF
4.86 MB Adobe PDF Visualizza/Apri
epi.15.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 4.87 MB
Formato Adobe PDF
4.87 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/424121
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact