Potential of CLSPN as a therapeutic target in melanoma: a key player in melanoma progression and tumor microenvironment

Abstract Background Melanoma is a highly aggressive form of skin cancer. Despite significant advances in targeted therapies and immunotherapeutic approaches, some patients still have poor response rates, making a deeper understanding of melanoma pathogenesis essential. Methods The expression of Claspin (CLSPN), prognosis and immune infiltration in skin cutaneous melanoma patients were analyzed by public databases. Immunohistochemistry was used to validate. Moreover, quantitative real-time polymerase chain reaction analysis, western blot, cell counting kit-8 assay, colony formation assay, flow cytometry, animal experiments, and RNA-seq were applied to explore its biological functions and potential molecular mechanisms of CLSPN in melanoma. Results Our results demonstrated that abnormal CLSPN expression was correlated with poor prognosis in melanoma. Meanwhile, CLSPN may promote melanoma growth and progression in vivo and in vitro through IFI44L/JAK/STAT1 signaling. Additionally, CLSPN was associated with negative immune microenvironment in melanoma and may be related to polarization of tumor associated macrophages towards M2-type. Conclusions These findings suggest that CLSPN may be a promising new target for melanoma and accelerate personalized therapeutic strategies. Graphical abstract