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CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity

Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression but remains poorly understood. We found that the uncharacterized epigenetic factor chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels cor...

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Autores principales: Siouda, Maha, Dujardin, Audrey D., Barbollat-Boutrand, Laetitia, Mendoza-Parra, Marco A., Gibert, Benjamin, Ouzounova, Maria, Bouaoud, Jebrane, Tonon, Laurie, Robert, Marie, Foy, Jean-Philippe, Lavergne, Vincent, Manie, Serge N., Viari, Alain, Puisieux, Alain, Ichim, Gabriel, Gronemeyer, Hinrich, Saintigny, Pierre, Mulligan, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251929/
https://www.ncbi.nlm.nih.gov/pubmed/32450513
http://dx.doi.org/10.1016/j.isci.2020.101141
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author Siouda, Maha
Dujardin, Audrey D.
Barbollat-Boutrand, Laetitia
Mendoza-Parra, Marco A.
Gibert, Benjamin
Ouzounova, Maria
Bouaoud, Jebrane
Tonon, Laurie
Robert, Marie
Foy, Jean-Philippe
Lavergne, Vincent
Manie, Serge N.
Viari, Alain
Puisieux, Alain
Ichim, Gabriel
Gronemeyer, Hinrich
Saintigny, Pierre
Mulligan, Peter
author_facet Siouda, Maha
Dujardin, Audrey D.
Barbollat-Boutrand, Laetitia
Mendoza-Parra, Marco A.
Gibert, Benjamin
Ouzounova, Maria
Bouaoud, Jebrane
Tonon, Laurie
Robert, Marie
Foy, Jean-Philippe
Lavergne, Vincent
Manie, Serge N.
Viari, Alain
Puisieux, Alain
Ichim, Gabriel
Gronemeyer, Hinrich
Saintigny, Pierre
Mulligan, Peter
author_sort Siouda, Maha
collection PubMed
description Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression but remains poorly understood. We found that the uncharacterized epigenetic factor chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels correlate with poor prognosis. Supporting a functional role for CDYL2 in malignancy, it positively regulated breast cancer cell migration, invasion, stem-like phenotypes, and epithelial-to-mesenchymal transition. CDYL2 regulation of these plasticity-associated processes depended on signaling via p65/NF-κB and STAT3. This, in turn, was downstream of CDYL2 regulation of MIR124 gene transcription. CDYL2 co-immunoprecipitated with G9a/EHMT2 and GLP/EHMT1 and regulated the chromatin enrichment of G9a and EZH2 at MIR124 genes. We propose that CDYL2 contributes to poor prognosis in breast cancer by recruiting G9a and EZH2 to epigenetically repress MIR124 genes, thereby promoting NF-κB and STAT3 signaling, as well as downstream cancer cell plasticity and malignant progression.
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spelling pubmed-72519292020-05-29 CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity Siouda, Maha Dujardin, Audrey D. Barbollat-Boutrand, Laetitia Mendoza-Parra, Marco A. Gibert, Benjamin Ouzounova, Maria Bouaoud, Jebrane Tonon, Laurie Robert, Marie Foy, Jean-Philippe Lavergne, Vincent Manie, Serge N. Viari, Alain Puisieux, Alain Ichim, Gabriel Gronemeyer, Hinrich Saintigny, Pierre Mulligan, Peter iScience Article Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression but remains poorly understood. We found that the uncharacterized epigenetic factor chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels correlate with poor prognosis. Supporting a functional role for CDYL2 in malignancy, it positively regulated breast cancer cell migration, invasion, stem-like phenotypes, and epithelial-to-mesenchymal transition. CDYL2 regulation of these plasticity-associated processes depended on signaling via p65/NF-κB and STAT3. This, in turn, was downstream of CDYL2 regulation of MIR124 gene transcription. CDYL2 co-immunoprecipitated with G9a/EHMT2 and GLP/EHMT1 and regulated the chromatin enrichment of G9a and EZH2 at MIR124 genes. We propose that CDYL2 contributes to poor prognosis in breast cancer by recruiting G9a and EZH2 to epigenetically repress MIR124 genes, thereby promoting NF-κB and STAT3 signaling, as well as downstream cancer cell plasticity and malignant progression. Elsevier 2020-05-06 /pmc/articles/PMC7251929/ /pubmed/32450513 http://dx.doi.org/10.1016/j.isci.2020.101141 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Siouda, Maha
Dujardin, Audrey D.
Barbollat-Boutrand, Laetitia
Mendoza-Parra, Marco A.
Gibert, Benjamin
Ouzounova, Maria
Bouaoud, Jebrane
Tonon, Laurie
Robert, Marie
Foy, Jean-Philippe
Lavergne, Vincent
Manie, Serge N.
Viari, Alain
Puisieux, Alain
Ichim, Gabriel
Gronemeyer, Hinrich
Saintigny, Pierre
Mulligan, Peter
CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity
title CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity
title_full CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity
title_fullStr CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity
title_full_unstemmed CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity
title_short CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity
title_sort cdyl2 epigenetically regulates mir124 to control nf-κb/stat3-dependent breast cancer cell plasticity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251929/
https://www.ncbi.nlm.nih.gov/pubmed/32450513
http://dx.doi.org/10.1016/j.isci.2020.101141
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