miR-146a-5p Promotes angiogenesis and confers Trastuzumab Resistance in HER2+ breast cancer

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• dc.contributor.author Cabello, Paula
• dc.contributor.author Torres-Ruiz, Sandra
• dc.contributor.author Adam-Artigues, Anna
• dc.contributor.author Forés-Martos, Jaume
• dc.contributor.author Martínez, María Teresa
• dc.contributor.author Hernando, Cristina
• dc.contributor.author Zazo, Sandra
• dc.contributor.author Madoz-Gúrpide, Juan
• dc.contributor.author Rovira, Ana
• dc.contributor.author Burgués, Octavio
• dc.contributor.author Rojo, Federico
• dc.contributor.author Albanell Mestres, Joan
• dc.contributor.author Lluch, Ana
• dc.contributor.author Bermejo, Begoña
• dc.contributor.author Cejalvo, Juan Miguel
• dc.contributor.author Eroles, Pilar
• dc.date.accessioned 2024-02-27T07:22:06Z
• dc.date.available 2024-02-27T07:22:06Z
• dc.date.issued 2023
• dc.description.abstract Trastuzumab treatment has significantly improved the prognosis of HER2-positive breast cancer patients. Despite this, resistance to therapy still remains the main clinical challenge. In order to evaluate the implication of microRNAs in the trastuzumab response, we performed a microRNA array in parental and acquired trastuzumab-resistant HER2-positive breast cancer cell lines. Our results identified miR-146a-5p as the main dysregulated microRNA. Interestingly, high miR-146a-5p expression in primary tumor tissue significantly correlated with shorter disease-free survival in HER2-positive breast cancer patients. The gain- and loss-of-function of miR-146a-5p modulated the response to trastuzumab. Furthermore, the overexpression of miR-146a-5p increased migration and angiogenesis, and promoted cell cycle progression by reducing CDKN1A expression. Exosomes from trastuzumab-resistant cells showed a high level of miR-146a-5p expression compared with the parental cells. In addition, the co-culture with resistant cells' exosomes was able to decrease in sensitivity and increase the migration capacities in trastuzumab-sensitive cells, as well as angiogenesis in HUVEC-2 cells. Collectively, these data support the role of miR-146a-5p in resistance to trastuzumab, and demonstrate that it can be transferred by exosomes conferring resistance properties to other cells.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cabello P, Torres-Ruiz S, Adam-Artigues A, Forés-Martos J, Martínez MT, Hernando C, Zazo S, Madoz-Gúrpide J, Rovira A, Burgués O, Rojo F, Albanell J, Lluch A, Bermejo B, Cejalvo JM, Eroles P. miR-146a-5p Promotes angiogenesis and confers Trastuzumab Resistance in HER2+ breast cancer. Cancers (Basel). 2023 Apr 4;15(7):2138. DOI: 10.3390/cancers15072138
• dc.identifier.doi http://dx.doi.org/10.3390/cancers15072138
• dc.identifier.issn 2072-6694
• dc.identifier.uri http://hdl.handle.net/10230/59268
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Cancers (Basel). 2023 Apr 4;15(7):2138
• dc.rights © 2023 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 (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword HER2+ breast cancer
• dc.subject.keyword Exosomes
• dc.subject.keyword miR-146a-5p
• dc.subject.keyword Resistance
• dc.subject.keyword Trastuzumab
• dc.title miR-146a-5p Promotes angiogenesis and confers Trastuzumab Resistance in HER2+ breast cancer
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion