Multiple roles of MicroRNAs in melanoma: biomarkers for diagnosis, prognosis, and treatment prediction

Melanoma, a highly malignant form of skin cancer, continues to rise in incidence worldwide. Early diagnosis and accurate prognostic assessment are critical to reducing melanoma-related mortality rates. MicroRNAs (miRNAs), a class of non-coding RNAs approximately 22 nucleotides in length, play pivotal roles in melanoma initiation, progression, invasion, and metastasis by regulating the expression of target genes. Beyond their cell-intrinsic functions, miRNAs are increasingly recognized as critical regulators of the tumor immune microenvironment (TIME). They modulate anti-tumor immune responses by influencing immune checkpoint expression, immune cell recruitment and function, and intercellular communication via extracellular vesicles (EVs). This comprehensive review explores the multifaceted functions of miRNAs in melanoma, highlighting their potential as diagnostic markers, prognostic indicators, and predictors of therapeutic response. It also addresses current research challenges and explores future directions, including the integration of AI-powered spatial transcriptomics to decipher the complex, context-dependent networks of miRNAs within the TIME, offering a theoretical foundation and novel insights for precision medicine in melanoma treatment.