| Texto completo | |
| Autor(es): |
Santos, Nathalia L.
;
Bustos, Silvina O.
;
Reis, Patricia P.
;
Chammas, Roger
;
Andrade, Luciana N. S.
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CELLS; v. 12, n. 9, p. 17-pg., 2023-05-05. |
| Resumo | |
Management of advanced melanoma remains challenging, with most BRAF (B-Raf proto-oncogene, serine/threonine kinase)-mutated metastatic patients relapsing within a few months upon MAPK inhibitors treatment. Modulation of tumor-derived extracellular vesicle (EVs) cargo with enrichment of antitumoral molecules is a promising strategy to impair tumor progression and increase treatment response. Herein, we report that restored expression of miR-195-5p, down-regulated in melanoma favoring drug resistance, increases the release of EVs enriched in the tumor suppressor miRNAs, miR-195-5p, miR-152-3p, and miR-202-3p. Incorporating these EVs by bystander tumor cells resulted in decreased proliferation and viability, accompanied by a reduction in CCND1 and YAP1 mRNA levels. Upon treatment with MAPK inhibitors, miR-195 EVs significantly decreased BCL2-L1 protein levels and increased cell death ratio and treatment efficacy. Additionally, EVs exogenously loaded with miR-195-5p by electroporation reduced tumor volume in vivo and impaired engraftment and growth of xenografts implanted with melanoma cells exposed to MAPK inhibitors. Our study shows that miR-195-5p antitumoral activity can be spread to bystander cells through EVs, improving melanoma response to targeted therapy and revealing a promising EV-based strategy to increase clinical response in patients harboring BRAF mutations. (AU) | |
| Processo FAPESP: | 19/07278-0 - Efeito da super-expressão do miR-195 na carga de microRNAs presentes em vesículas extracelulares secretadas por células de melanoma humano e na regulação da sensibilidade ao tratamento alvo-dirigido via transferência horizontal de informação |
| Beneficiário: | Nathalia Leal Santos |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |