Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

The identification of liquid biomarkers remains a major challenge to improve thediagnosis of melanoma patients with brain metastases. Circulating miRNAs packaged into tumorsecreted small extracellular vesicles (sEVs) contribute to tumor progression. To investigate therelease of tumor-secreted miRNAs by brain metastasis, we developed a xenograft model wherehuman metastatic melanoma cells were injected intracranially in nude mice. The comprehensiveprofiles of both free miRNAs and those packaged in sEVs secreted by the melanoma cells in theplasma demonstrated that most (80%) of the sEV-associated miRNAs were also present in serumEVs from a cohort of metastatic melanomas, included in a publicly available dataset. Remarkably,among them, we found three miRNAs (miR-224-5p, miR-130a-3p and miR-21-5p) in sEVs showinga trend of upregulation during melanoma progression. Our model is proven to be valuable foridentifying miRNAs in EVs that are unequivocally secreted by melanoma cells in the brain andcould be associated to disease progression