DHX37 and tumor growth: a novel avenue for melanoma research.

INTRODUCTION: This study explores a novel mechanism by which the RNA helicase DHX37 contributes to melanoma and elucidates the reasons for resistance to tumor immunotherapy, providing new insights for the treatment of melanoma. METHOD: This study integrated multiomics data for systematic analysis. The prognostic value of the candidate differentially expressed genes was assessed on the basis of public databases. Single-cell transcriptome data were used to determine the expression patterns of key genes and elucidate intercellular communication networks. Finally, in vitro and in vivo experiments confirmed the mechanism of action of DHX37 in melanoma. RESULTS: Ten key candidate genes that were differentially expressed between primary and metastatic melanoma were identified. Among them, the RNA helicase DHX37 was significantly overexpressed in metastatic tissues, and its high expression was significantly associated with poor overall survival (OS) and shorter progression-free survival (PFS). Functional enrichment analysis revealed that high DHX37 expression was closely related to DNA repair and immune response pathways. Immunological analysis revealed that high DHX37 expression was associated with the formation of an immunosuppressive microenvironment. Single-cell analysis further revealed that DHX37 was specifically expressed primarily in melanoma cells and endothelial cells. In vitro experiments confirmed that knockdown of the DHX37 gene in melanoma cells significantly inhibited tumor cell proliferation and migration. Coculturing DHX37 knockdown melanoma cells with CD8 + T cells significantly increased the secretion of related cytokines. Animal experiments demonstrated that DHX37 knockdown in melanoma cells resulted in smaller tumors and more related immune cytokines. CONCLUSION: This study systematically identified the multiple functions of DHX37 in melanoma progression, suggesting that DHX37 can serve as a potential prognostic biomarker and therapeutic target, providing new insights for precision therapy in melanoma.