This study aims to elucidate the role of minichromosome maintenance protein 4 (MCM4) in malignant melanoma (MM) and explore the underlying mechanism. Initially, data from The Cancer Genome Atlas (TCGA) database and the Molecular Signature Database (MSigDB) were used to investigate the biological impact of MCM4 on MM. Further, a prognostic model using Cox regression analysis was developed to predict the overall survival (OS) rate in the MM patients. The effects of MCM4 on the proliferation, migration, and invasion abilities of MM (B16F0 and A375) cells were demonstrated using the CCK‐8, colony formation, EDU, wound scratch, and Transwell assays. In subcutaneous tumor models in C57BL/6 mice in vivo, the expression levels of MCM4 in MM cells and tumors were detected using Western blot and immunofluorescence approaches. The bioinformatics analysis indicated that MCM4 was expressed higher in MM tissues than in the normal tissues (p < 0.05). The established OS prediction model could significantly contribute to devising follow‐up strategies and treating MM patients. MCM4 knockdown resulted in reduced proliferation, migration, and invasion abilities of MM cells, which were reversed by MCM4 overexpression (p < 0.05). Moreover, MCM4 could activate the phosphatidylinositol 3′‐kinase (PI3K)/AKT pathway in MM cells. The PI3K inhibitor (LY294002) could reverse the effects of MCM4 on MM cells. MCM4 could substantially prompt the tumor growth of MM in mice through the PI3K/AKT pathway in vivo. In summary, MCM4 prompted the development and metastasis of MM by activating the PI3K/AKT pathway.

中文翻译：

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MCM4 通过激活 PI3K/AKT 通路促进恶性黑色素瘤的进展


本研究旨在阐明微染色体维持蛋白 4 （MCM4） 在恶性黑色素瘤 （MM） 中的作用，并探讨其潜在机制。最初，来自癌症基因组图谱 （TCGA） 数据库和分子特征数据库 （MSigDB） 的数据用于研究 MCM4 对 MM 的生物学影响。此外，开发了一种使用 Cox 回归分析的预后模型来预测 MM 患者的总生存率 （OS）。使用 CCK-8、集落形成、EDU、伤口划痕和 Transwell 测定证明了 MCM4 对 MM （B16F0 和 A375） 细胞增殖、迁移和侵袭能力的影响。在 C57BL/6 小鼠体内皮下肿瘤模型中，使用 Western blot 和免疫荧光方法检测 MM 细胞和肿瘤中 MCM4 的表达水平。生物信息学分析表明，MCM4 在 MM 组织中的表达高于正常组织 （p < 0.05）。已建立的 OS 预测模型可显着有助于制定随访策略和治疗 MM 患者。MCM4 敲低导致 MM 细胞的增殖、迁移和侵袭能力降低，这被 MCM4 过表达逆转 （p < 0.05）。此外，MCM4 可以激活 MM 细胞中的磷脂酰肌醇 3′-激酶 （PI3K）/AKT 通路。PI3K 抑制剂 （LY294002） 可以逆转 MCM4 对 MM 细胞的影响。MCM4 可通过体内 PI3K/AKT 通路显著促进小鼠 MM 的肿瘤生长。综上所述，MCM4 通过激活 PI3K/AKT 通路促进 MM 的发生和转移。