Extracellular Vesicle-Packaged miR-195-5p Sensitizes Melanoma to Targeted Therapy with Kinase Inhibitors

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorSantos, Nathalia L.-
Autor(es): dc.creatorBustos, Silvina O.-
Autor(es): dc.creatorReis, Patricia P.-
Autor(es): dc.creatorChammas, Roger-
Autor(es): dc.creatorAndrade, Luciana N. S.-
Data de aceite: dc.date.accessioned2025-08-21T17:33:59Z-
Data de disponibilização: dc.date.available2025-08-21T17:33:59Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-05-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cells12091317-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/248830-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/248830-
Descrição: dc.descriptionManagement 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.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionCenter for Translational Research in Oncology (LIM24) Instituto do Câncer do Estado de São Paulo Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Comprehensive Center for Precision Oncology Universidade de São Paulo-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics and Experimental Research Unity (UNIPEX) Faculdade de Medicina Universidade Estadual Paulista (UNESP)-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics and Experimental Research Unity (UNIPEX) Faculdade de Medicina Universidade Estadual Paulista (UNESP)-
Descrição: dc.descriptionFAPESP: 2019/07278-0-
Descrição: dc.descriptionCNPq: 305700/2017-0-
Idioma: dc.languageen-
Relação: dc.relationCells-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectextracellular vesicles-
Palavras-chave: dc.subjectMAPK inhibitors-
Palavras-chave: dc.subjectmelanoma-
Palavras-chave: dc.subjectmiR-195-5p-
Título: dc.titleExtracellular Vesicle-Packaged miR-195-5p Sensitizes Melanoma to Targeted Therapy with Kinase Inhibitors-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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