Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer

The anti-HER2 monoclonal antibody trastuzumab and new derivative formulations are the standard treatment for HER2-positive breast cancer. However, after 1 to 5 years of treatment, some patients acquire resistance to therapy, leading to relapse. The microRNA-449 family members were downregulated in H...

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Autores: Lameirinhas, Ana, Torres-Ruiz, Sandra, Garrido-Cano, Iris, Hernando, Cristina, Martínez, María Teresa, Rovira, Ana, Albanell Mestres, Joan, Zazo, Sandra, Rojo, Federico, Bermejo, Begoña, Lluch, Ana, Cejalvo, Juan Miguel, Tormo, Eduardo, Eroles, Pilar
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:dnet:rdupf_______::dd33b3078b3a35e4e30ed7f73924cf6d
Acesso em linha:https://hdl.handle.net/10230/73383
http://dx.doi.org/10.1186/s10020-025-01163-z
Access Level:acceso abierto
Palavra-chave:Breast cancer
FASN
HER2
Trastuzumab
microRNAs-449
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spelling Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancerLameirinhas, AnaTorres-Ruiz, SandraGarrido-Cano, IrisHernando, CristinaMartínez, María TeresaRovira, AnaAlbanell Mestres, JoanZazo, SandraRojo, FedericoBermejo, BegoñaLluch, AnaCejalvo, Juan MiguelTormo, EduardoEroles, PilarBreast cancerFASNHER2TrastuzumabmicroRNAs-449The anti-HER2 monoclonal antibody trastuzumab and new derivative formulations are the standard treatment for HER2-positive breast cancer. However, after 1 to 5 years of treatment, some patients acquire resistance to therapy, leading to relapse. The microRNA-449 family members were downregulated in HER2-positive breast cancer cell lines and low levels were associated with patients¿ worse prognosis. Moreover, trastuzumab-resistant HER2-positive breast cancer cell lines showed lower microRNAs-449 and higher Fatty Acid Synthase (FASN) expression, compared to sensitive cell lines. The direct regulation of FASN by microRNA-449a and microRNA-449b-5p was demonstrated. Moreover, microRNAs-449 overexpression and FASN inhibition decreased cell proliferation and sensitized cells to trastuzumab treatment by inhibiting the PI3K/AKT signaling pathway. Together, these results suggest the microRNAs-449/FASN axis as a potential therapeutic target in combination with anti-HER2 agents to overcome trastuzumab resistance and to improve treatment response in HER2-positive breast cancer patients.BioMed Central2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/10230/73383http://dx.doi.org/10.1186/s10020-025-01163-zreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésMolecular Medicine. 2025;31(1):116© The Author(s) 2025. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:rdupf_______::dd33b3078b3a35e4e30ed7f73924cf6d2026-06-12T07:21:37Z
dc.title.none.fl_str_mv Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
title Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
spellingShingle Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
Lameirinhas, Ana
Breast cancer
FASN
HER2
Trastuzumab
microRNAs-449
title_short Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
title_full Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
title_fullStr Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
title_full_unstemmed Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
title_sort Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer
dc.creator.none.fl_str_mv Lameirinhas, Ana
Torres-Ruiz, Sandra
Garrido-Cano, Iris
Hernando, Cristina
Martínez, María Teresa
Rovira, Ana
Albanell Mestres, Joan
Zazo, Sandra
Rojo, Federico
Bermejo, Begoña
Lluch, Ana
Cejalvo, Juan Miguel
Tormo, Eduardo
Eroles, Pilar
author Lameirinhas, Ana
author_facet Lameirinhas, Ana
Torres-Ruiz, Sandra
Garrido-Cano, Iris
Hernando, Cristina
Martínez, María Teresa
Rovira, Ana
Albanell Mestres, Joan
Zazo, Sandra
Rojo, Federico
Bermejo, Begoña
Lluch, Ana
Cejalvo, Juan Miguel
Tormo, Eduardo
Eroles, Pilar
author_role author
author2 Torres-Ruiz, Sandra
Garrido-Cano, Iris
Hernando, Cristina
Martínez, María Teresa
Rovira, Ana
Albanell Mestres, Joan
Zazo, Sandra
Rojo, Federico
Bermejo, Begoña
Lluch, Ana
Cejalvo, Juan Miguel
Tormo, Eduardo
Eroles, Pilar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Breast cancer
FASN
HER2
Trastuzumab
microRNAs-449
topic Breast cancer
FASN
HER2
Trastuzumab
microRNAs-449
description The anti-HER2 monoclonal antibody trastuzumab and new derivative formulations are the standard treatment for HER2-positive breast cancer. However, after 1 to 5 years of treatment, some patients acquire resistance to therapy, leading to relapse. The microRNA-449 family members were downregulated in HER2-positive breast cancer cell lines and low levels were associated with patients¿ worse prognosis. Moreover, trastuzumab-resistant HER2-positive breast cancer cell lines showed lower microRNAs-449 and higher Fatty Acid Synthase (FASN) expression, compared to sensitive cell lines. The direct regulation of FASN by microRNA-449a and microRNA-449b-5p was demonstrated. Moreover, microRNAs-449 overexpression and FASN inhibition decreased cell proliferation and sensitized cells to trastuzumab treatment by inhibiting the PI3K/AKT signaling pathway. Together, these results suggest the microRNAs-449/FASN axis as a potential therapeutic target in combination with anti-HER2 agents to overcome trastuzumab resistance and to improve treatment response in HER2-positive breast cancer patients.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
2026
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 https://hdl.handle.net/10230/73383
http://dx.doi.org/10.1186/s10020-025-01163-z
url https://hdl.handle.net/10230/73383
http://dx.doi.org/10.1186/s10020-025-01163-z
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Molecular Medicine. 2025;31(1):116
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 BioMed Central
publisher.none.fl_str_mv BioMed Central
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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