MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway.

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-11-06 DOI:10.1002/tox.24433
Xuewei Zhang, Mingming Dong, Guoxing Zheng, Meng Sun, Chuzhao Zhang, Zibin Zhou, Shijie Tang
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Abstract

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.

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MCM4 通过激活 PI3K/AKT 通路促进恶性黑色素瘤的进展
本研究旨在阐明迷你染色体维护蛋白4(MCM4)在恶性黑色素瘤(MM)中的作用并探索其潜在机制。最初,研究人员利用癌症基因组图谱(TCGA)数据库和分子特征数据库(MSigDB)中的数据研究了MCM4对MM的生物学影响。此外,还利用 Cox 回归分析建立了一个预后模型,以预测 MM 患者的总生存率(OS)。利用 CCK-8、集落形成、EDU、伤口划痕和 Transwell 试验证明了 MCM4 对 MM(B16F0 和 A375)细胞增殖、迁移和侵袭能力的影响。在 C57BL/6 小鼠皮下肿瘤模型中,使用 Western 印迹和免疫荧光方法检测了 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
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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