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HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells

Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architect...

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Autores principales: Penzo, Carlotta, Arnoldo, Laura, Pegoraro, Silvia, Petrosino, Sara, Ros, Gloria, Zanin, Rossella, Wiśniewski, Jacek R., Manfioletti, Guidalberto, Sgarra, Riccardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721465/
https://www.ncbi.nlm.nih.gov/pubmed/31382504
http://dx.doi.org/10.3390/cancers11081105
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author Penzo, Carlotta
Arnoldo, Laura
Pegoraro, Silvia
Petrosino, Sara
Ros, Gloria
Zanin, Rossella
Wiśniewski, Jacek R.
Manfioletti, Guidalberto
Sgarra, Riccardo
author_facet Penzo, Carlotta
Arnoldo, Laura
Pegoraro, Silvia
Petrosino, Sara
Ros, Gloria
Zanin, Rossella
Wiśniewski, Jacek R.
Manfioletti, Guidalberto
Sgarra, Riccardo
author_sort Penzo, Carlotta
collection PubMed
description Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architectural chromatin transcription factor that alters DNA structure and interacts with transcription factors favouring their landing onto transcription regulatory sequences. Here, we provide evidence of an additional mechanism exploited by HMGA1 to modulate transcription. We demonstrate that, in a triple-negative breast cancer cellular model, HMGA1 sustains the action of epigenetic modifiers and in particular it positively influences both histone H3S10 phosphorylation by ribosomal protein S6 kinase alpha-3 (RSK2) and histone H2BK5 acetylation by CREB-binding protein (CBP). HMGA1, RSK2, and CBP control the expression of a set of genes involved in tumor progression and epithelial to mesenchymal transition. These results suggest that HMGA1 has an effect on the epigenetic status of cancer cells and that it could be exploited as a responsiveness predictor for epigenetic therapies in triple-negative breast cancers.
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spelling pubmed-67214652019-09-10 HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells Penzo, Carlotta Arnoldo, Laura Pegoraro, Silvia Petrosino, Sara Ros, Gloria Zanin, Rossella Wiśniewski, Jacek R. Manfioletti, Guidalberto Sgarra, Riccardo Cancers (Basel) Article Chromatin accessibility plays a critical factor in regulating gene expression in cancer cells. Several factors, including the High Mobility Group A (HMGA) family members, are known to participate directly in chromatin relaxation and transcriptional activation. The HMGA1 oncogene encodes an architectural chromatin transcription factor that alters DNA structure and interacts with transcription factors favouring their landing onto transcription regulatory sequences. Here, we provide evidence of an additional mechanism exploited by HMGA1 to modulate transcription. We demonstrate that, in a triple-negative breast cancer cellular model, HMGA1 sustains the action of epigenetic modifiers and in particular it positively influences both histone H3S10 phosphorylation by ribosomal protein S6 kinase alpha-3 (RSK2) and histone H2BK5 acetylation by CREB-binding protein (CBP). HMGA1, RSK2, and CBP control the expression of a set of genes involved in tumor progression and epithelial to mesenchymal transition. These results suggest that HMGA1 has an effect on the epigenetic status of cancer cells and that it could be exploited as a responsiveness predictor for epigenetic therapies in triple-negative breast cancers. MDPI 2019-08-02 /pmc/articles/PMC6721465/ /pubmed/31382504 http://dx.doi.org/10.3390/cancers11081105 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Penzo, Carlotta
Arnoldo, Laura
Pegoraro, Silvia
Petrosino, Sara
Ros, Gloria
Zanin, Rossella
Wiśniewski, Jacek R.
Manfioletti, Guidalberto
Sgarra, Riccardo
HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
title HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
title_full HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
title_fullStr HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
title_full_unstemmed HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
title_short HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells
title_sort hmga1 modulates gene transcription sustaining a tumor signalling pathway acting on the epigenetic status of triple-negative breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721465/
https://www.ncbi.nlm.nih.gov/pubmed/31382504
http://dx.doi.org/10.3390/cancers11081105
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