Portal de investigación
MiRNA-449 family is epigenetically repressed and sensitizes to doxorubicin through ACSL4 downregulation in triple-negative breast cancer
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Garrido-Cano, I
- Rojo, F
- Tormo, E
Grupos y Plataformas de I+D+i
Abstract
Despite progress in breast cancer treatment, a significant portion of patients still relapse because of drug resistance. The involvement of microRNAs in cancer progression and chemotherapy response is well established. Therefore, this study aimed to elucidate the dysregulation of the microRNA-449 family (specifically, microRNA-449a, microRNA-449b-5p, and microRNA-449c-5p) and its impact on resistance to doxorubicin, a commonly used chemotherapeutic drug for the treatment of triple-negative breast cancer. We found that the microRNA-449 family is downregulated in triple-negative breast cancer and demonstrated its potential as a diagnostic biomarker. Besides, our findings indicate that the downregulation of the microRNA-449 family is mediated by the microRNAs-449/SIRT1-HDAC1 negative feedback loop. Moreover, it was found that the microRNA-449 family dysregulates the fatty acid metabolism by targeting ACSL4, which is a potential prognostic biomarker that mediates doxorubicin response through regulation of the drug extrusion pump ABCG2. Altogether, our results suggest that the microRNA-449 family might be a potential therapeutic target for the treatment of triple-negative breast cancer since it is implicated in doxorubicin response through ACSL4/ABCG2 axis regulation. Ultimately, our results also highlight the value of microRNAs-449 and ACSL4 as diagnostic and prognostic biomarkers in triple-negative breast cancer.
© 2024. The Author(s).
Datos de la publicación
- ISSN/ISSNe:
- 2058-7716, 2058-7716
- Tipo:
- Article
- Páginas:
- 372-372
- PubMed:
- 39174500
Cell Death Discovery SPRINGERNATURE
Citas Recibidas en Web of Science: 4
Documentos
- No hay documentos
Filiaciones
Financiación
Proyectos y Estudios Clínicos
Modulación de la respuesta al tratamiento anti-HER2 mediante regulación del microentorno tumoral.
Investigador Principal: SANDRA TORRES RUIZ
ACIF/2019/119 . CONSELLERIA EDUCACION/INNOVACION,UNIVERSIDADES, CIENCIA Y SOCIEDAD DIGITAL/EMPLEO . 2019
Predicción de enfermedad residual después de la terapia neoadyuvante en cáncer de mama HER2 positivo e identificación de estrategias para superar la resistencia.
Investigador Principal: PILAR EROLES ASENSIO
PI21/01351 . INSTITUTO SALUD CARLOS III . 2022
Cita
MiRNA-449 family is epigenetically repressed and sensitizes to doxorubicin through ACSL4 downregulation in triple-negative breast cancer. Torres S, Garrido I, Lameirinhas A, Burgués O, Hernando C, Martínez MT, Rojo F et al. Cell Death Discovery. 2024 agosto 22. 10 (1):372-372. DOI:10.1038/s41420-024-02128-7. PMID:39174500.
