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Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression

FRA1 (FOSL1) is a transcription factor and a member of the activator protein-1 superfamily. FRA1 is expressed in most tissues at low levels, and its expression is robustly induced in response to extracellular signals, leading to downstream cellular processes. However, abnormal FRA1 overexpression ha...

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Autores principales: Al-khayyat, Wuroud, Pirkkanen, Jake, Dougherty, Jessica, Laframboise, Taylor, Dickinson, Noah, Khaper, Neelam, Lees, Simon J., Mendonca, Marc S., Boreham, Douglas R., Tai, Tze Chun, Thome, Christopher, Tharmalingam, Sujeenthar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571788/
https://www.ncbi.nlm.nih.gov/pubmed/37830558
http://dx.doi.org/10.3390/cells12192344
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author Al-khayyat, Wuroud
Pirkkanen, Jake
Dougherty, Jessica
Laframboise, Taylor
Dickinson, Noah
Khaper, Neelam
Lees, Simon J.
Mendonca, Marc S.
Boreham, Douglas R.
Tai, Tze Chun
Thome, Christopher
Tharmalingam, Sujeenthar
author_facet Al-khayyat, Wuroud
Pirkkanen, Jake
Dougherty, Jessica
Laframboise, Taylor
Dickinson, Noah
Khaper, Neelam
Lees, Simon J.
Mendonca, Marc S.
Boreham, Douglas R.
Tai, Tze Chun
Thome, Christopher
Tharmalingam, Sujeenthar
author_sort Al-khayyat, Wuroud
collection PubMed
description FRA1 (FOSL1) is a transcription factor and a member of the activator protein-1 superfamily. FRA1 is expressed in most tissues at low levels, and its expression is robustly induced in response to extracellular signals, leading to downstream cellular processes. However, abnormal FRA1 overexpression has been reported in various pathological states, including tumor progression and inflammation. To date, the molecular effects of FRA1 overexpression are still not understood. Therefore, the aim of this study was to investigate the transcriptional and functional effects of FRA1 overexpression using the CGL1 human hybrid cell line. FRA1-overexpressing CGL1 cells were generated using stably integrated CRISPR-mediated transcriptional activation, resulting in a 2–3 fold increase in FRA1 mRNA and protein levels. RNA-sequencing identified 298 differentially expressed genes with FRA1 overexpression. Gene ontology analysis showed numerous molecular networks enriched with FRA1 overexpression, including transcription-factor binding, regulation of the extracellular matrix and adhesion, and a variety of signaling processes, including protein kinase activity and chemokine signaling. In addition, cell functional assays demonstrated reduced cell adherence to fibronectin and collagen with FRA1 overexpression and altered cell cycle progression. Taken together, this study unravels the transcriptional response mediated by FRA1 overexpression and establishes the role of FRA1 in adhesion and cell cycle progression.
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spelling pubmed-105717882023-10-14 Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression Al-khayyat, Wuroud Pirkkanen, Jake Dougherty, Jessica Laframboise, Taylor Dickinson, Noah Khaper, Neelam Lees, Simon J. Mendonca, Marc S. Boreham, Douglas R. Tai, Tze Chun Thome, Christopher Tharmalingam, Sujeenthar Cells Article FRA1 (FOSL1) is a transcription factor and a member of the activator protein-1 superfamily. FRA1 is expressed in most tissues at low levels, and its expression is robustly induced in response to extracellular signals, leading to downstream cellular processes. However, abnormal FRA1 overexpression has been reported in various pathological states, including tumor progression and inflammation. To date, the molecular effects of FRA1 overexpression are still not understood. Therefore, the aim of this study was to investigate the transcriptional and functional effects of FRA1 overexpression using the CGL1 human hybrid cell line. FRA1-overexpressing CGL1 cells were generated using stably integrated CRISPR-mediated transcriptional activation, resulting in a 2–3 fold increase in FRA1 mRNA and protein levels. RNA-sequencing identified 298 differentially expressed genes with FRA1 overexpression. Gene ontology analysis showed numerous molecular networks enriched with FRA1 overexpression, including transcription-factor binding, regulation of the extracellular matrix and adhesion, and a variety of signaling processes, including protein kinase activity and chemokine signaling. In addition, cell functional assays demonstrated reduced cell adherence to fibronectin and collagen with FRA1 overexpression and altered cell cycle progression. Taken together, this study unravels the transcriptional response mediated by FRA1 overexpression and establishes the role of FRA1 in adhesion and cell cycle progression. MDPI 2023-09-24 /pmc/articles/PMC10571788/ /pubmed/37830558 http://dx.doi.org/10.3390/cells12192344 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Al-khayyat, Wuroud
Pirkkanen, Jake
Dougherty, Jessica
Laframboise, Taylor
Dickinson, Noah
Khaper, Neelam
Lees, Simon J.
Mendonca, Marc S.
Boreham, Douglas R.
Tai, Tze Chun
Thome, Christopher
Tharmalingam, Sujeenthar
Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression
title Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression
title_full Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression
title_fullStr Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression
title_full_unstemmed Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression
title_short Overexpression of FRA1 (FOSL1) Leads to Global Transcriptional Perturbations, Reduced Cellular Adhesion and Altered Cell Cycle Progression
title_sort overexpression of fra1 (fosl1) leads to global transcriptional perturbations, reduced cellular adhesion and altered cell cycle progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571788/
https://www.ncbi.nlm.nih.gov/pubmed/37830558
http://dx.doi.org/10.3390/cells12192344
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