Malignant melanoma is one of the most aggressive of cancers; if not treated early, it can metastasize rapidly. Therefore, drug therapy plays an important role in the treatment of melanoma. Cinobufagin, an active ingredient derived from Venenum bufonis, can inhibit the growth and development of melanoma. However, the mechanism underlying its therapeutic effects is unclear. The purpose of this study was to predict the potential targets of cinobufagin in melanoma. We gathered known and predicted targets for cinobufagin from four online databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were then performed. Gene expression data were downloaded from the GSE46517 dataset, and differential gene expression analysis and weighted gene correlation network analysis were performed to identify melanoma-related genes. Using input melanoma-related genes and drug targets in the STRING online database and applying molecular complex detection (MCODE) analysis, we identified key targets that may be the potential targets of cinobufagin in melanoma. Moreover, we assessed the distribution of the pharmacological targets of cinobufagin in melanoma key clusters using single-cell data from the GSE215120 dataset obtained from the Gene Expression Omnibus database. The crucial targets of cinobufagin in melanoma were identified from the intersection of key clusters with melanoma-related genes and drug targets. Receiver operating characteristic curve (ROC) analysis, survival analysis, molecular docking, and molecular dynamics simulation were performed to gain further insights. Our findings suggest that cinobufagin may affect melanoma by arresting the cell cycle by inhibiting three protein tyrosine/serine kinases (EGFR, ERBB2, and CDK2). However, our conclusions are not supported by relevant experimental data and require further study.

中文翻译：

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基于网络药理学、单细胞RNA测序数据、分子对接和分子动力学模拟探讨华蟾素治疗黑色素瘤的作用机制


恶性黑色素瘤是最具侵袭性的癌症之一。如果不及早治疗，它会迅速转移。因此，药物治疗在黑色素瘤的治疗中起着重要的作用。华蟾素是从蟾蜍中提取的活性成分，可以抑制黑色素瘤的生长和发展。然而，其治疗作用的机制尚不清楚。本研究的目的是预测华蟾素在黑色素瘤中的潜在靶点。我们从四个在线数据库中收集了华蟾素的已知和预测靶标。然后进行基因本体（GO）分析和京都基因和基因组百科全书（KEGG）富集分析。从GSE46517数据集中下载基因表达数据，并进行差异基因表达分析和加权基因相关网络分析，以确定黑色素瘤相关基因。利用STRING在线数据库中输入的黑色素瘤相关基因和药物靶点，并应用分子复合物检测（MCODE）分析，我们确定了可能是华蟾素治疗黑色素瘤的潜在靶点的关键靶点。此外，我们使用从基因表达综合数据库获得的 GSE215120 数据集中的单细胞数据评估了华蟾​​素的药理靶点在黑色素瘤关键簇中的分布。华蟾素在黑色素瘤中的关键靶标是通过关键簇与黑色素瘤相关基因和药物靶标的交叉点确定的。进行受试者工作特征曲线（ROC）分析、生存分析、分子对接和分子动力学模拟以获得进一步的见解。我们的研究结果表明，华蟾素可能通过抑制三种蛋白酪氨酸/丝氨酸激酶（EGFR、ERBB2 和 CDK2）来阻止细胞周期，从而影响黑色素瘤。 然而，我们的结论没有相关实验数据的支持，需要进一步研究。