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Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells

BACKGROUND: In breast cancer, the epithelial to mesenchyme transition (EMT) is associated to tumour dissemination, drug resistance and high relapse risks. It is partly controlled by epigenetic modifications such as histone acetylation and methylation. The identification of genes involved in these re...

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Autores principales: Gregoire, Jean-Marc, Fleury, Laurence, Salazar-Cardozo, Clara, Alby, Frédéric, Masson, Véronique, Arimondo, Paola Barbara, Ausseil, Frédéric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006536/
https://www.ncbi.nlm.nih.gov/pubmed/27581651
http://dx.doi.org/10.1186/s12885-016-2683-5
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author Gregoire, Jean-Marc
Fleury, Laurence
Salazar-Cardozo, Clara
Alby, Frédéric
Masson, Véronique
Arimondo, Paola Barbara
Ausseil, Frédéric
author_facet Gregoire, Jean-Marc
Fleury, Laurence
Salazar-Cardozo, Clara
Alby, Frédéric
Masson, Véronique
Arimondo, Paola Barbara
Ausseil, Frédéric
author_sort Gregoire, Jean-Marc
collection PubMed
description BACKGROUND: In breast cancer, the epithelial to mesenchyme transition (EMT) is associated to tumour dissemination, drug resistance and high relapse risks. It is partly controlled by epigenetic modifications such as histone acetylation and methylation. The identification of genes involved in these reversible modifications represents an interesting therapeutic strategy to fight metastatic disease by inducing mesenchymal cell differentiation to an epithelial phenotype. METHODS: We designed a siRNA library based on chromatin modification-related to functional domains and screened it in the mesenchymal breast cancer cell line MDA-MB-231. The mesenchyme to epithelium transition (MET) activation was studied by following human E-CADHERIN (E-CAD) induction, a specific MET marker, and cell morphology. Candidate genes were validated by studying the expression of several differential marker genes and their impact on cell migration. RESULTS: The screen led to the identification of 70 gene candidates among which some are described to be, directly or indirectly, involved in EMT like ZEB1, G9a, SMAD5 and SMARCD3. We also identified the DOT1L as involved in EMT regulation in MDA-MB-231. Moreover, for the first time, KAT5 gene was linked to the maintenance of the mesenchymal phenotype. CONCLUSIONS: A multi-parametric RNAi screening approach was developed to identify new EMT regulators such as KAT5 in the triple negative breast cancer cell line MDA-MB-231. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2683-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-50065362016-09-01 Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells Gregoire, Jean-Marc Fleury, Laurence Salazar-Cardozo, Clara Alby, Frédéric Masson, Véronique Arimondo, Paola Barbara Ausseil, Frédéric BMC Cancer Research Article BACKGROUND: In breast cancer, the epithelial to mesenchyme transition (EMT) is associated to tumour dissemination, drug resistance and high relapse risks. It is partly controlled by epigenetic modifications such as histone acetylation and methylation. The identification of genes involved in these reversible modifications represents an interesting therapeutic strategy to fight metastatic disease by inducing mesenchymal cell differentiation to an epithelial phenotype. METHODS: We designed a siRNA library based on chromatin modification-related to functional domains and screened it in the mesenchymal breast cancer cell line MDA-MB-231. The mesenchyme to epithelium transition (MET) activation was studied by following human E-CADHERIN (E-CAD) induction, a specific MET marker, and cell morphology. Candidate genes were validated by studying the expression of several differential marker genes and their impact on cell migration. RESULTS: The screen led to the identification of 70 gene candidates among which some are described to be, directly or indirectly, involved in EMT like ZEB1, G9a, SMAD5 and SMARCD3. We also identified the DOT1L as involved in EMT regulation in MDA-MB-231. Moreover, for the first time, KAT5 gene was linked to the maintenance of the mesenchymal phenotype. CONCLUSIONS: A multi-parametric RNAi screening approach was developed to identify new EMT regulators such as KAT5 in the triple negative breast cancer cell line MDA-MB-231. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2683-5) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-31 /pmc/articles/PMC5006536/ /pubmed/27581651 http://dx.doi.org/10.1186/s12885-016-2683-5 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gregoire, Jean-Marc
Fleury, Laurence
Salazar-Cardozo, Clara
Alby, Frédéric
Masson, Véronique
Arimondo, Paola Barbara
Ausseil, Frédéric
Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
title Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
title_full Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
title_fullStr Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
title_full_unstemmed Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
title_short Identification of epigenetic factors regulating the mesenchyme to epithelium transition by RNA interference screening in breast cancer cells
title_sort identification of epigenetic factors regulating the mesenchyme to epithelium transition by rna interference screening in breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006536/
https://www.ncbi.nlm.nih.gov/pubmed/27581651
http://dx.doi.org/10.1186/s12885-016-2683-5
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