Portal de investigación
miR-146a-5p Promotes Angiogenesis and Confers Trastuzumab Resistance in HER2+Breast Cancer
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Zazo, Sandra
- Madoz-Gurpide, Juan
- Rovira, Ana
- Rojo, Federico
- Albanell, Joan
Grupos y Plataformas de I+D+i
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.
Datos de la publicación
- ISSN/ISSNe:
- 2072-6694, 2072-6694
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 37046799
Cancers MDPI
Citas Recibidas en Web of Science: 17
Documentos
Filiaciones
Keywords
- HER2+breast cancer; resistance; miR-146a-5p; trastuzumab; exosomes
Financiación
Proyectos y Estudios Clínicos
Caracterizacion y repercusion terapeutica de la ecologia de cancer de mama HER2 positivo
Investigador Principal: PILAR EROLES ASENSIO
PI18/01219 . INSTITUTO SALUD CARLOS III . 2019
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
miR-146a-5p Promotes Angiogenesis and Confers Trastuzumab Resistance in HER2+Breast Cancer. Cabello P, Torres S, Adam A, Fores J, Martinez MT, Hernando C, Zazo S et al. Cancers. 2023 abril 01. 15 (7):DOI:10.3390/cancers15072138. PMID:37046799.
