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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

Grant number: 19/07278-0
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2019
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Roger Chammas
Grantee:Nathalia Leal Santos
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Melanoma is considered the most aggressive form of skin cancer. About 60% of the patients harbor a mutation in the BRAF gene, resulting in constitutive activation of the mitogen-activated protein kinase (MAPK) pathway. Combined targeted therapy with BRAF and MEK inhibitors is associated with significant improvement in progression-free survival and objective responses of patients with advanced melanoma. Extracellular vesicles (EVs) are nanometric particles that act in the intercellular communication by transferring bioactive molecules including proteins, lipids and nucleic acids. MicroRNAs are small, non-coding RNAs capable of regulate gene expression at the post-transcriptional level in a sequence-specific manner. The transfer of microRNAs through EVs plays important roles in cancer development and progression. MicroRNA-195 is among the microRNAs associated with the progression of melanoma. This miR acts as an antiproliferative factor and its expression is down-regulated when compared to melanocytes. We observed in a pilot study that the super-expression of miR-195 in the lineage of metastatic melanoma SKMel05 increases the amount of EVs secreted and that these particles are capable of inhibit the viability of naive cells. Based on the above considerations, the aim of this study is to evaluate the effect of these EVs on the regulation of sensibility to target-therapy and the relation of this effect with their microRNA cargo. Furthermore, it is intended to evaluate if the induction of the re-expression of miR-195 represents a new strategy for the treatment of melanoma.