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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Detalles Bibliográficos
Autores: Lameirinhas, A, Torres-Ruiz, S, Garrido-Cano, I, Hernando, C, Martínez, MT, Rovira, A, Albanell, J, Zazo, S, Rojo, F, Bermejo, B, Lluch, A, Cejalvo, JM, Tormo, E, Eroles, P
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p19943
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/19943
Access Level:acceso abierto
Palabra clave:Breast cancer
HER2
microRNAs-449
FASN
Trastuzumab
Descripción
Sumario: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.

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