Background Melanoma is among the most aggressive types of skin malignancy and can have an unpredictable clinical course. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma. Methods HSDL2 protein levels were examined by immunohistochemistry. The roles of HSDL2 in cell proliferation and apoptosis were identified by CCK-8 and colony formation assays. The function of HSDL2 in cell apoptosis was analysed by flow cytometry. Western blotting, cell proliferation and apoptosis and a xenograft tumour model were utilized to explore the inhibitory functions and mechanisms of CuE in melanoma. Results HSDL2 is overexpressed in melanoma and promotes melanoma progression by activating the ERK and AKT pathways. CuE could inhibit the ERK and AKT pathways by decreasing HSDL2 expression; therefore, CuE could inhibit melanoma growth in vitro and in vivo. Conclusion HSDL2 may be a promising therapeutic target against melanoma, and CuE can inhibit melanoma by downregulating HSDL2 expression.

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Background Cutaneous melanoma (CM) has an overall poor prognosis due to a high rate of metastasis. This study aimed to explore the role of hypoxia-related genes (HRGs) in CM. Methods We first used on-negative matrix factorization consensus clustering (NMF) to cluster CM samples and preliminarily analyzed the relationship of HRGs to CM prognosis and immune cell infiltration. Subsequently, we identified prognostic-related hub genes by univariate COX regression analysis and the least absolute shrinkage and selection operator (LASSO) and constructed a prognostic model. Finally, we calculated a risk score for patients with CM and investigated the relationship between the risk score and potential surrogate markers of response to immune checkpoint inhibitors (ICIs), such as TMB, IPS values, and TIDE scores. Results Through NMF clustering, we identified high expression of HRGs as a risk factor for the prognosis of CM patients, and at the same time, increased expression of HRGs also indicated a poorer immune microenvironment. Subsequently, we identified eight gene signatures (FBP1, NDRG1, GPI, IER3, B4GALNT2, BGN, PKP1, and EDN2) by LASSO regression analysis and constructed a prognostic model. Conclusion Our study identifies the prognostic significance of hypoxia-related genes in melanoma and shows a novel eight-gene signature to predict the potential efficacy of ICIs.