Cargando…

HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A

Tumor suppressor ARID1A, a subunit of the chromatin remodeling complex SWI/SNF, regulates cell cycle progression, interacts with the tumor suppressor TP53, and prevents genomic instability. In addition, ARID1A has been shown to foster resistance to cancer therapy. By promoting non-homologous end joi...

Descripción completa

Detalles Bibliográficos
Autores principales: Andrade, Daniel, Mehta, Meghna, Griffith, James, Oh, Sangphil, Corbin, Joshua, Babu, Anish, De, Supriyo, Chen, Allshine, Zhao, Yan D., Husain, Sanam, Roy, Sudeshna, Xu, Liang, Aube, Jeffrey, Janknecht, Ralf, Gorospe, Myriam, Herman, Terence, Ramesh, Rajagopal, Munshi, Anupama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966656/
https://www.ncbi.nlm.nih.gov/pubmed/31847141
http://dx.doi.org/10.3390/cancers11122014
_version_ 1783488787104399360
author Andrade, Daniel
Mehta, Meghna
Griffith, James
Oh, Sangphil
Corbin, Joshua
Babu, Anish
De, Supriyo
Chen, Allshine
Zhao, Yan D.
Husain, Sanam
Roy, Sudeshna
Xu, Liang
Aube, Jeffrey
Janknecht, Ralf
Gorospe, Myriam
Herman, Terence
Ramesh, Rajagopal
Munshi, Anupama
author_facet Andrade, Daniel
Mehta, Meghna
Griffith, James
Oh, Sangphil
Corbin, Joshua
Babu, Anish
De, Supriyo
Chen, Allshine
Zhao, Yan D.
Husain, Sanam
Roy, Sudeshna
Xu, Liang
Aube, Jeffrey
Janknecht, Ralf
Gorospe, Myriam
Herman, Terence
Ramesh, Rajagopal
Munshi, Anupama
author_sort Andrade, Daniel
collection PubMed
description Tumor suppressor ARID1A, a subunit of the chromatin remodeling complex SWI/SNF, regulates cell cycle progression, interacts with the tumor suppressor TP53, and prevents genomic instability. In addition, ARID1A has been shown to foster resistance to cancer therapy. By promoting non-homologous end joining (NHEJ), ARID1A enhances DNA repair. Consequently, ARID1A has been proposed as a promising therapeutic target to sensitize cancer cells to chemotherapy and radiation. Here, we report that ARID1A is regulated by human antigen R (HuR), an RNA-binding protein that is highly expressed in a wide range of cancers and enables resistance to chemotherapy and radiation. Our results indicate that HuR binds ARID1A mRNA, thereby increasing its stability in breast cancer cells. We further find that ARID1A expression suppresses the accumulation of DNA double-strand breaks (DSBs) caused by radiation and can rescue the loss of radioresistance triggered by HuR inhibition, suggesting that ARID1A plays an important role in HuR-driven resistance to radiation. Taken together, our work shows that HuR and ARID1A form an important regulatory axis in radiation resistance that can be targeted to improve radiotherapy in breast cancer patients.
format Online
Article
Text
id pubmed-6966656
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-69666562020-02-04 HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A Andrade, Daniel Mehta, Meghna Griffith, James Oh, Sangphil Corbin, Joshua Babu, Anish De, Supriyo Chen, Allshine Zhao, Yan D. Husain, Sanam Roy, Sudeshna Xu, Liang Aube, Jeffrey Janknecht, Ralf Gorospe, Myriam Herman, Terence Ramesh, Rajagopal Munshi, Anupama Cancers (Basel) Article Tumor suppressor ARID1A, a subunit of the chromatin remodeling complex SWI/SNF, regulates cell cycle progression, interacts with the tumor suppressor TP53, and prevents genomic instability. In addition, ARID1A has been shown to foster resistance to cancer therapy. By promoting non-homologous end joining (NHEJ), ARID1A enhances DNA repair. Consequently, ARID1A has been proposed as a promising therapeutic target to sensitize cancer cells to chemotherapy and radiation. Here, we report that ARID1A is regulated by human antigen R (HuR), an RNA-binding protein that is highly expressed in a wide range of cancers and enables resistance to chemotherapy and radiation. Our results indicate that HuR binds ARID1A mRNA, thereby increasing its stability in breast cancer cells. We further find that ARID1A expression suppresses the accumulation of DNA double-strand breaks (DSBs) caused by radiation and can rescue the loss of radioresistance triggered by HuR inhibition, suggesting that ARID1A plays an important role in HuR-driven resistance to radiation. Taken together, our work shows that HuR and ARID1A form an important regulatory axis in radiation resistance that can be targeted to improve radiotherapy in breast cancer patients. MDPI 2019-12-13 /pmc/articles/PMC6966656/ /pubmed/31847141 http://dx.doi.org/10.3390/cancers11122014 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
Andrade, Daniel
Mehta, Meghna
Griffith, James
Oh, Sangphil
Corbin, Joshua
Babu, Anish
De, Supriyo
Chen, Allshine
Zhao, Yan D.
Husain, Sanam
Roy, Sudeshna
Xu, Liang
Aube, Jeffrey
Janknecht, Ralf
Gorospe, Myriam
Herman, Terence
Ramesh, Rajagopal
Munshi, Anupama
HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A
title HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A
title_full HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A
title_fullStr HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A
title_full_unstemmed HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A
title_short HuR Reduces Radiation-Induced DNA Damage by Enhancing Expression of ARID1A
title_sort hur reduces radiation-induced dna damage by enhancing expression of arid1a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966656/
https://www.ncbi.nlm.nih.gov/pubmed/31847141
http://dx.doi.org/10.3390/cancers11122014
work_keys_str_mv AT andradedaniel hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT mehtameghna hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT griffithjames hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT ohsangphil hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT corbinjoshua hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT babuanish hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT desupriyo hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT chenallshine hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT zhaoyand hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT husainsanam hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT roysudeshna hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT xuliang hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT aubejeffrey hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT janknechtralf hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT gorospemyriam hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT hermanterence hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT rameshrajagopal hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a
AT munshianupama hurreducesradiationinduceddnadamagebyenhancingexpressionofarid1a