MicroRNAs as Diagnostic and Prognostic Biomarkers in Melanoma and Non-Melanoma Skin Cancers: An Updated Review

MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators in melanoma and non-melanoma skin cancers (NMSCs), yet their full biological and clinical significance remains incompletely defined. This review synthesizes current evidence on miRNA dysregulation across basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), Merkel cell carcinoma (MCC), and melanoma, emphasizing their diagnostic, prognostic, and therapeutic relevance. In BCC, distinct miRNA expression signatures differentiate tumor tissue from normal skin and correlate with histopathological subtypes. miR-383-5p, miR-4705, miR-145-5p, and miR-18a show strong diagnostic potential, while downregulation of miR-34a is consistently associated with greater tumor aggressiveness. Subtype-specific profiles further delineate superficial versus infiltrative lesions, highlighting miRNAs as markers of tumor behavior. cSCC similarly demonstrates characteristic miRNA alterations. miR-31 is markedly upregulated during the transition from actinic keratosis to invasive carcinoma, whereas high miR-205 and low miR-203 levels correlate with poor and favorable prognosis, respectively. Regarding MCC, many miRNAs such as miR-375 and miR-182 may present a clinical value for potential biomarkers, as they are upregulated in MCC. Merkel cell carcinoma has also been linked with Merkel cell polyomavirus (MCPyV). Melanoma exhibits a complex miRNA landscape, including oncogenic miR-18a-5p and miR-146a, and tumor-suppressive miR-128-3p. Several miRNAs correlate with metastatic potential, BRAF mutation status, and therapeutic resistance, particularly miR-181a/b, underscoring their potential as predictive biomarkers. Overall, current evidence supports miRNAs as promising diagnostic, prognostic, and predictive biomarkers in cutaneous oncology. Standardized methodologies and large-scale validation remain essential for their integration into routine clinical practice.