Abstract
Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer arising from the malignant transformation of melanocytes. The incidence has risen in recent decades, significantly impacting patients’ quality of life and straining healthcare systems. Existing prognostic biomarkers for SKCM are not accurate enough, emphasizing the urgent need for new biomarkers and therapeutic targets. This study comprehensively explored the role of Melan-A (MLANA) in SKCM through bioinformatics analysis and in-vitro experiments. Results showed that MLANA is overexpressed in SKCM tissues, significantly linked to Breslow depth, and associated with poor patient prognosis. Functional assays revealed that interfering with MLANA expression inhibits melanoma cell proliferation, migration, and invasion, while inducing apoptosis and G1/S phase arrest. Immune infiltration analysis revealed a negative correlation between high MLANA expression and the infiltration levels of various immune cells, indicating that MLANA may facilitate SKCM progression by altering the tumor microenvironment. The study highlights MLANA’s biological importance in SKCM, suggesting its potential as a prognostic biomarker and immunotherapy target, thereby providing new insights for SKCM diagnosis and treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-026-02078-7.