黑色素瘤是一种高致死率的原发性恶性肿瘤，好发于皮肤和眼组织，而黑色素瘤发生的分子机制仍知之甚少。在这里，我们发现黑色素瘤组织中死亡相关蛋白样 1 (DAPL1) 的表达低于癌旁组织或痣组织，并且 DAPL1 表达较低的葡萄膜黑色素瘤患者的生存率低于 DAPL1 表达较高的患者。 DAPL1 的过度表达会抑制培养的黑色素瘤细胞的增殖，而 DAPL1 的敲低则会增加细胞增殖。肿瘤移植实验结果还表明，DAPL1在体内抑制裸鼠视网膜下和皮下组织中黑色素瘤细胞的肿瘤发生。最后，DAPL1 通过减少泛素介导的 P21 降解并促进其稳定性来增加 P21 的蛋白水平，从而抑制黑色素瘤细胞的增殖。相反，P21 的敲除中和了 DAPL1 抑制对黑色素瘤细胞增殖的影响，并增强了黑色素瘤肿瘤发生的严重性。这些结果表明 DAPL1 是一种新型黑色素瘤肿瘤抑制基因，因此是黑色素瘤的潜在治疗靶点。© 2024。作者。

Melanoma is a primary malignant tumor with high lethality, which occurs in the skin and eye tissues, while the molecular mechanisms of melanomagenesis remain largely unknown. Here, we show that death-associated protein-like 1 (DAPL1) expression is lower in melanoma tissues than in paracancerous tissues or nevus tissues, and Uveal melanoma patients with lower DAPL1 expression have a poorer survival rate than those with higher expression of DAPL1. Overexpression of DAPL1 inhibits proliferation of cultured melanoma cells, whereas knockdown of DAPL1 increases cell proliferation. Tumor transplantation experiment results also demonstrate that DAPL1 inhibits tumorigenesis of melanoma cells both in subretinal and subcutaneous tissues of nude mice in vivo. Finally, DAPL1 inhibits proliferation of melanoma cells by increasing the protein level of P21 via decreasing the ubiquitin mediated degradation of P21 and promoting its stability. Conversely, knockdown of P21 neutralizes the effects of inhibition of DAPL1 on melanoma cell proliferation and enhances the severity of melanoma tumorigenesis. These results suggest that DAPL1 is a novel melanoma tumor suppressor gene and thus a potential therapeutic target for melanoma.© 2024. The Author(s).