| Autor: |
Paula Cabello, Sandra Torres-Ruiz, Anna Adam-Artigues, Jaume Forés-Martos, María Teresa Martínez, Cristina Hernando, Sandra Zazo, Juan Madoz-Gúrpide, Ana Rovira, Octavio Burgués, Federico Rojo, Joan Albanell, Ana Lluch, Begoña Bermejo, Juan Miguel Cejalvo, Pilar Eroles |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cancers; Volume 15; Issue 7; Pages: 2138 |
| ISSN: |
2072-6694 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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