Introduction: The prevalence of colon cancer remains high across the world. The early diagnosis of colon cancer is challenging. Moreover, patients with colon cancer frequently suffer from poor prognoses. Methods: Differentially expressed genes (DEGs) in colon cancer were acquired based on TCGA-COAD dataset screening. DEGs were input into the Connectivity Map (CMap) database to screen small molecule compounds with the potential to reverse colon cancer pathological function. Glycitein ranked first among the screened small molecule compounds. We downloaded the main targets of glycitein from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database and constructed protein-protein interaction (PPI) networks of those which were closely related to targets by Search Tool for the Retrieval of Interaction Gene/Proteins (STRING). Five potential targets of glycitein for treating colon cancer were identified (CCNA2, ESR1, ESR2, MAPK14, and PTGS2). These targets were used as seeds for random walk with restart (RWR) analysis of PPI networks. Then, the interaction network of glycitein-colon cancer-related genes was constructed based on the top 50 genes in affinity coefficients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the potential genes targeted by glycitein in colon cancer treatment and those were closely bound up with targets. Results: GO analysis demonstrated that the enrichment of these genes was primarily discovered in biological functions including regulation of fibroblast proliferation, response to oxygen levels, and epithelial cell proliferation. KEGG analysis results illustrated that the signaling pathways where these genes were mostly involved consisted of the mitogen-activated protein kinases signaling pathway, the phosphatidylinositol-3-kinase-Akt signaling pathway, and the p53 signaling pathway. Finally, stable binding of glycitein to five potential targets in colon cancer was verified by molecular docking. Conclusion: This study elucidated the key targets and main pathways of glycitein on the basis of network pharmacology and preliminarily analyzed molecular mechanisms in the treatment of colon cancer. A scientific basis is provided for glycitein application in treating colon cancer.


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基于网络药理学和分子对接的大豆黄素治疗结肠癌机制

简介：结肠癌的患病率在世界范围内仍然很高。结肠癌的早期诊断具有挑战性。此外，结肠癌患者往往预后不佳。方法：基于TCGA-COAD数据集筛选获得结肠癌中的差异表达基因（DEGs）。将 DEG 输入连接图 (CMap) 数据库以筛选具有逆转结肠癌病理功能潜力的小分子化合物。Glycitein在筛选的小分子化合物中排名第一。我们从中药系统药理学数据库和分析平台数据库中下载了黄豆黄素的主要靶点，并通过相互作用基因/蛋白质检索工具（STRING）构建了与靶点密切相关的蛋白质-蛋白质相互作用（PPI）网络。 ）。确定了用于治疗结肠癌的 5 个黄豆黄素潜在靶标（CCNA2、ESR1、ESR2、MAPK14 和 PTGS2）。这些目标被用作对 PPI 网络进行重新启动 (RWR) 分析的随机游走的种子。然后，基于亲和系数排名前50位的基因构建大豆黄素-结肠癌相关基因的相互作用网络。基因本体论（GO）和京都基因和基因组百科全书（KEGG）对黄豆黄素在结肠癌治疗中靶向的潜在基因进行了富集分析，这些基因与目标密切相关。结果：GO分析表明，这些基因的富集主要体现在生物学功能中，包括调节成纤维细胞增殖、对氧水平的反应和上皮细胞增殖。KEGG分析结果表明，这些基因主要参与的信号通路包括丝裂原活化蛋白激酶信号通路、磷脂酰肌醇-3-激酶-Akt信号通路和p53信号通路。最后，通过分子对接验证了大豆黄素与结肠癌中五个潜在靶标的稳定结合。结论：本研究以网络药理学为基础，阐明黄豆黄素的关键靶点和主要通路，初步分析其在结肠癌治疗中的分子机制。为黄豆黄素在结肠癌治疗中的应用提供了科学依据。