The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors

The mechanisms of chemotherapy resistance in triple negative breast cancer remain unclear, and so, new molecules which might mediate this resistance could optimize treatment response. Here we analyzed the involvement of the miRNA-449 family in the response to doxorubicin. The cell viability, cell-cy...

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Autores: Tormo, Eduardo, Ballester, Sandra, Adam-Artigues, Anna, Burgués, Octavio, Alonso, Elisa, Bermejo, Begoña, Menendez Romero, Silvia, Zazo, Sandra, Madoz-Gúrpide, Juan, Rovira Guerín, Ana, Albanell Mestres, Joan, Rojo, Federico, Lluch, Ana, Eroles, Pilar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44316
Acceso en línea:http://hdl.handle.net/10230/44316
http://dx.doi.org/10.1038/s41598-019-41472-y
Access Level:acceso abierto
Palabra clave:Mama -- Càncer -- Aspectes genètics
Mama -- Càncer -- Tractament
id ES_794fdb02fba2cd237b63d712ac7b97b9
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spelling The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factorsTormo, EduardoBallester, SandraAdam-Artigues, AnnaBurgués, OctavioAlonso, ElisaBermejo, BegoñaMenendez Romero, SilviaZazo, SandraMadoz-Gúrpide, JuanRovira Guerín, AnaAlbanell Mestres, JoanRojo, FedericoLluch, AnaEroles, PilarMama -- Càncer -- Aspectes genèticsMama -- Càncer -- TractamentThe mechanisms of chemotherapy resistance in triple negative breast cancer remain unclear, and so, new molecules which might mediate this resistance could optimize treatment response. Here we analyzed the involvement of the miRNA-449 family in the response to doxorubicin. The cell viability, cell-cycle phases, and the expression of in silico target genes and proteins of sensitive/resistant triple negative breast cancer cell lines were evaluated in response to doxorubicin treatment and after gain/loss of miRNAs-449 function achieved by transient transfection. Triple negative breast cancer patients were selected for ex vivo experiments and to evaluate gene and miRNAs expression changes after treatment, as well as survival analysis by Kaplan-Meier. Doxorubicin treatment upregulated miRNAs-449 and DNA-damage responder factors E2F1 and E2F3 in triple negative breast cancer sensitive breast cancer cells, while expression remained unaltered in resistant ones. In vitro overexpression of miRNAs-449 sensitized cells to the treatment and significantly reduced the resistance to doxorubicin. These changes showed also a strong effect on cell cycle regulation. Finally, elevated levels of miRNA-449a associated significantly with better survival in chemotherapy-treated triple negative breast cancer patients. These results reveal for the first time the involvement of the miRNA-449 family in doxorubicin resistance and their predictive and prognostic value in triple negative breast cancer patients.Nature Research202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44316http://dx.doi.org/10.1038/s41598-019-41472-yreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésScientific Reports. 2019 Mar 29;9(1):5316Copyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/443162026-06-12T07:21:37Z
dc.title.none.fl_str_mv The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
title The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
spellingShingle The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
Tormo, Eduardo
Mama -- Càncer -- Aspectes genètics
Mama -- Càncer -- Tractament
title_short The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
title_full The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
title_fullStr The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
title_full_unstemmed The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
title_sort The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors
dc.creator.none.fl_str_mv Tormo, Eduardo
Ballester, Sandra
Adam-Artigues, Anna
Burgués, Octavio
Alonso, Elisa
Bermejo, Begoña
Menendez Romero, Silvia
Zazo, Sandra
Madoz-Gúrpide, Juan
Rovira Guerín, Ana
Albanell Mestres, Joan
Rojo, Federico
Lluch, Ana
Eroles, Pilar
author Tormo, Eduardo
author_facet Tormo, Eduardo
Ballester, Sandra
Adam-Artigues, Anna
Burgués, Octavio
Alonso, Elisa
Bermejo, Begoña
Menendez Romero, Silvia
Zazo, Sandra
Madoz-Gúrpide, Juan
Rovira Guerín, Ana
Albanell Mestres, Joan
Rojo, Federico
Lluch, Ana
Eroles, Pilar
author_role author
author2 Ballester, Sandra
Adam-Artigues, Anna
Burgués, Octavio
Alonso, Elisa
Bermejo, Begoña
Menendez Romero, Silvia
Zazo, Sandra
Madoz-Gúrpide, Juan
Rovira Guerín, Ana
Albanell Mestres, Joan
Rojo, Federico
Lluch, Ana
Eroles, Pilar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mama -- Càncer -- Aspectes genètics
Mama -- Càncer -- Tractament
topic Mama -- Càncer -- Aspectes genètics
Mama -- Càncer -- Tractament
description The mechanisms of chemotherapy resistance in triple negative breast cancer remain unclear, and so, new molecules which might mediate this resistance could optimize treatment response. Here we analyzed the involvement of the miRNA-449 family in the response to doxorubicin. The cell viability, cell-cycle phases, and the expression of in silico target genes and proteins of sensitive/resistant triple negative breast cancer cell lines were evaluated in response to doxorubicin treatment and after gain/loss of miRNAs-449 function achieved by transient transfection. Triple negative breast cancer patients were selected for ex vivo experiments and to evaluate gene and miRNAs expression changes after treatment, as well as survival analysis by Kaplan-Meier. Doxorubicin treatment upregulated miRNAs-449 and DNA-damage responder factors E2F1 and E2F3 in triple negative breast cancer sensitive breast cancer cells, while expression remained unaltered in resistant ones. In vitro overexpression of miRNAs-449 sensitized cells to the treatment and significantly reduced the resistance to doxorubicin. These changes showed also a strong effect on cell cycle regulation. Finally, elevated levels of miRNA-449a associated significantly with better survival in chemotherapy-treated triple negative breast cancer patients. These results reveal for the first time the involvement of the miRNA-449 family in doxorubicin resistance and their predictive and prognostic value in triple negative breast cancer patients.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44316
http://dx.doi.org/10.1038/s41598-019-41472-y
url http://hdl.handle.net/10230/44316
http://dx.doi.org/10.1038/s41598-019-41472-y
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Scientific Reports. 2019 Mar 29;9(1):5316
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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