MicroRNAs in Cutaneous Melanoma: Biological Roles, Clinical Utility, and Future Directions

Cutaneous melanoma remains a malignancy with substantial metastatic potential, and conventional diagnostic and surveillance tools such as biopsy and imaging have recognized limitations in sensitivity, specificity, and invasiveness. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers because of their stability in body fluids and their disease-specific expression patterns. This narrative review summarizes current evidence on the biological roles of miRNAs in melanoma, acting as either oncogenes or tumor suppressors, and their potential clinical utility across diagnosis, prognosis, treatment monitoring, and therapeutic targeting. Individual circulating miRNAs (e.g., miR-21, miR-221, miR-206, miR-125b) and multi-miRNA signatures (e.g., MEL12, MEL38, MELmiR-7) have shown associations with tumor stage, recurrence, and survival, and several panels have demonstrated high diagnostic sensitivity and specificity in liquid biopsy assays. miRNAs also participate in drug resistance and immune modulation, suggesting relevance to immune checkpoint inhibitor therapy and potential as therapeutic targets. However, clinical translation remains limited by the lack of standardized isolation and quantification protocols, tumor and patient heterogeneity, and the predominantly associative nature of current evidence. Continued methodological standardization, larger validation cohorts, and integration with other omics platforms will be needed before circulating miRNAs can be incorporated into routine melanoma management.