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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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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. |
format | Online Article Text |
id | pubmed-7251929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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