Circulating microRNA enriched in plasma small extracellular vesicles profiling in a preclinical model of metastatic human melanoma in the mouse brain

Patients with melanoma brain metastases have a dismal prognosis, with a median overall survival of 6 months. The identification of non-invasive, easily-manageable biomarkers, which reflect the progression of metastatic melanoma, remains a major challenge to integrate prognosis and improve diagnosis. Circulating miRNAs packed into tumor-released small extracellular vesicles (sEVs) have been shown to contribute to tumor initiation and metastasis formation. Their relative stability and easy detection in human body fluids make them suitable for use as liquid biomarkers.We analyzed by next-generation sequencing the expression profile of circulating miRNAs both freely in the plasma and packed in the purified sEVs of athymic mice bearing metastatic melanoma in the brain. We characterized the isolated sEVs for surface EV-specific surface markers (CD81, CD9), morphology and size/amount. Here, we identified a small set of circulating miRNAs (hsa-miR-224-5p, hsa-miR-130a-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-29a-3p and hsa-miR-29b-3p) contained in sEVs that correlates with the development and progression of melanoma metastatic disease. We underline the usefulness of our preclinical experimental model to identify more clearly miRNAs uniquely released by cancer cells. Our data further support the emerging role of liquid biopsy for detection of metastatic melanoma in the brain.