Zhao Yurong, Tao Shuaixian, Wang Qiang, Liu Yan, Yang Wenke, Zhang Shoude, Su Zhanhai, Ma Xueman
Graduate School of Qinghai University, Xining, China.
Medical School of Qinghai University, Xining, China.
Transl Cancer Res. 2022 May;11(5):1195-1206. doi: 10.21037/tcr-22-667.
The purpose of this study was to investigate the mechanism of action of muscone on breast cancer using network pharmacology and molecular docking techniques.
Targets of muscone acid action were collected using the PubChem and SwissTargetPrediction databases. Relevant target sets of breast cancer were collected using the GeneCards database, and the intersection of the drug-disease targets was used as the potential target of muscone action in breast cancer. The STRING database was used to construct a target protein-protein interaction (PPI) network, and the data were imported into Cytoscape 3.7.1 for topological network analysis to obtain the core target genes of muscone in breast cancer. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. The correlation of core gene expression with breast cancer survival was analyzed using the online Kaplan-Meier plotter tool. Molecular docking of core target genes to muscone was performed using AutoDock Vina.
A total of 18 common targets of muscone and breast cancer were obtained through target intersection. The PPI map and topology analysis revealed that androgen receptor (AR), progesterone receptor (PGR), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2), heat shock protein 90 alpha family class A member 1 (HSP90AA1), mitogen-activated protein kinase 14 (MAPK14), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) might be the key targets of muscone acting on breast cancer. The GO enrichment analysis identified 60 terms, while the KEGG pathway enrichment analysis identified 7 signaling pathways, including steroid hormone biosynthesis, ovarian steroidogenesis, cancer pathways, and the tumor necrosis factor (TNF) signaling pathway. The results of survival stage analysis showed that the binding activity between muskone and key targets was better than other targets. The molecular docking results showed that muscone had the highest docking affinity for the key target gene at -7.0 kJ/moL.
Muscone might exert anti-breast cancer effects through cancer pathways, ovarian steroidogenesis, and TNF signaling pathways and has the potential to be developed as a clinical agent.
本研究旨在运用网络药理学和分子对接技术探究麝香酮对乳腺癌的作用机制。
通过PubChem和SwissTargetPrediction数据库收集麝香酮酸作用的靶点。利用GeneCards数据库收集乳腺癌的相关靶点集，并将药物 - 疾病靶点的交集作为麝香酮在乳腺癌中作用的潜在靶点。使用STRING数据库构建靶点蛋白 - 蛋白相互作用（PPI）网络，并将数据导入Cytoscape 3.7.1进行拓扑网络分析，以获取麝香酮在乳腺癌中的核心靶点基因。使用DAVID数据库进行基因本体论（GO）功能富集和京都基因与基因组百科全书（KEGG）通路富集分析。使用在线Kaplan - Meier绘图工具分析核心基因表达与乳腺癌生存的相关性。使用AutoDock Vina对核心靶点基因与麝香酮进行分子对接。
通过靶点交集共获得18个麝香酮与乳腺癌的共同靶点。PPI图谱和拓扑分析显示，雄激素受体（AR）、孕激素受体（PGR）、基质金属蛋白酶9（MMP9）、前列腺素 - 内过氧化物合酶2（PTGS2）、热休克蛋白90α家族A类成员1（HSP90AA1）、丝裂原活化蛋白激酶14（MAPK14）和细胞色素P450家族19亚家族A成员1（CYP19A1）可能是麝香酮作用于乳腺癌的关键靶点。GO富集分析确定了60个术语，KEGG通路富集分析确定了7条信号通路，包括类固醇激素生物合成、卵巢类固醇生成、癌症通路和肿瘤坏死因子（TNF）信号通路。生存阶段分析结果表明，麝香酮与关键靶点之间的结合活性优于其他靶点。分子对接结果显示，麝香酮对关键靶点基因的对接亲和力最高，为 -7.0 kJ/moL。
麝香酮可能通过癌症通路、卵巢类固醇生成和TNF信号通路发挥抗乳腺癌作用，具有开发为临床药物的潜力。
