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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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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. |
format | Online Article Text |
id | pubmed-5006536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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