| Full text | |
| Author(s): |
Santos, Nathalia L.
;
Bustos, Silvina O.
;
Reis, Patricia P.
;
Chammas, Roger
;
Andrade, Luciana N. S.
Total Authors: 5
|
| Document type: | Journal article |
| Source: | CELLS; v. 12, n. 9, p. 17-pg., 2023-05-05. |
| Abstract | |
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) | |
| FAPESP's process: | 19/07278-0 - Effect of miR-195 superexpression in the cargo of microRNAs present in extracellular vesicles secreted by human melanoma cells and in the regulation of sensibility to target-therapy through horizontal transfer of information |
| Grantee: | Nathalia Leal Santos |
| Support Opportunities: | Scholarships in Brazil - Master |