TMT proteomics reveals that miR-425-5p promotes proliferation and metastasis of malignant melanoma by inhibiting SCARA5

While the relationship between miRNAs and malignant melanoma is well-established, the role of miR-425-5p in melanoma remains underexplored. This study investigated the molecular mechanisms underlying miR-425-5p-mediated regulation of malignant melanoma proliferation and metastasis, with emphasis on its interaction with scavenger receptor class A member 5 (SCARA5). The impact of SCARA5 and miR-425-5p on melanoma cell proliferation and metastatic potential was assessed using CCK-8, clonogenic, scratch, and Transwell assays. Western blotting was employed to quantify apoptosis markers, epithelial-mesenchymal transition (EMT)-related proteins, and components of the Akt signaling pathway. Bioinformatics and dual-luciferase reporter assays validated the direct interaction between miR-425-5p and SCARA5. In vivo, a subcutaneous tumor model in nude mice was used to evaluate tumor growth, and TUNEL staining was performed to assess apoptosis. Tandem Mass Tag (TMT) proteomics was applied to comprehensively identify downstream pathways modulated by miR-425-5p. Silencing SCARA5 in A375 and A2058 cells downregulated the expression of caspase-3 and E-cadherin levels while elevating Bcl-2, p-AKT, N-cadherin, β-catenin, and ZEB1 levels. Conversely, SCARA5 overexpression reversed these effects. Dual-luciferase assays confirmed that miR-425-5p could directly target SCARA5. Inhibition of miR-425-5p expression increased SCARA5 expression and suppressed proliferation/metastasis, whereas miR-425-5p mimics reduced SCARA5 expression and enhanced malignancy. In the in vivo model, SCARA5 overexpression significantly inhibited tumor growth, while the administration of miR-425-5p agonists promoted it. Proteomics further revealed that miR-425-5p could suppress the PPARγ pathway and activate the AKT signaling pathway. Our findings demonstrate that miR-425-5p promotes melanoma progression by downregulating SCARA5, thereby inhibiting apoptosis, activating AKT phosphorylation, and inducing EMT. These findings identify the miR-425-5p/SCARA5 axis as a potential therapeutic target for melanoma.