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

• DOI: 10.1186/s10020-025-01163-z
• Publication Date: 2025-03-26T02:59:05Z
• Authors: Ana Lameirinhas; Sandra Torres-Ruiz; Iris Garrido-Cano; Cristina Hernando; María Teresa Mart...; Ana Rovira; Joan Albanell; Sandra Zazo; Federico Rojo; Begoña Bermejo; Ana Lluch; Juan Miguel Cejalvo; Eduardo Tormo; Pilar Eroles

Abstract 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 therapy, leading relapse. microRNA-449 family members were downregulated in cancer cell lines low levels associated with patients’ worse prognosis. Moreover, trastuzumab-resistant showed lower microRNAs-449 higher Fatty Acid Synthase (FASN) expression, compared sensitive lines. direct regulation FASN by microRNA-449a microRNA-449b-5p was demonstrated. overexpression inhibition decreased proliferation sensitized cells inhibiting PI3K/AKT signaling pathway. Together, these results suggest microRNAs-449/FASN axis as a potential therapeutic target combination agents overcome improve response patients.