miRNAs bridging the gap between the tumor microenvironment and liquid biopsy in cutaneous melanoma.

Cutaneous melanoma remains one of the most challenging neoplasms and the deadliest form of skin cancer. miRNAs are a class of non-coding RNA molecules found in both tissues and body fluids that can negatively regulate gene expression in eukaryotic cells, playing key roles in health and disease. Dysregulated miRNA levels have been linked to various aspects of melanocytic tumor biology, including the transition from benign to malignant stages, immunosuppression, dissemination, and therapy resistance. Here, we provide a timely review of the roles of miRNAs within the cutaneous melanoma tumor microenvironment, emphasizing their impact on immune cell phenotypes and functions, angiogenesis, innate and adaptive immunity, and immune checkpoint expression to help refine future biomarkers and therapeutic targets in the field. We will also address their roles in circular and long non-coding RNA sponging interactions and the potential for translating miRNAs into clinical practice, given their simultaneous presence in both cutaneous melanoma tissues and liquid biopsies. The main challenges and limitations associated with such a translational approach will also be addressed.