Ma Zushuai, Ji Yanrong, Zhao Chengdu, Zhu Xu, Ding Qianshan
{"title":"网络药理学方法与加权基因共表达网络分析相结合,发现CDKN2A是常卫清治疗结直肠癌的关键靶点。","authors":"Ma Zushuai, Ji Yanrong, Zhao Chengdu, Zhu Xu, Ding Qianshan","doi":"10.1186/s41065-025-00405-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Changweiqing (CWQ) is a Chinese herbal formula for the treatment of the gastrointestinal tract diseases, but its role in the treatment of colorectal cancer (CRC) has not been clarified. This study aimed to explore the molecular mechanism of CWQ in CRC treatment through bioinformatics analysis and network pharmacology.</p><p><strong>Methods: </strong>Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction database were used to collect the bioactive components of CWQ. The databases including DisgeNET, GeneCards, MalaCards, Online Mendelian Inheritance in Man and Comparative Toxicogenomics were used to obtain CRC-related targets. The Cancer Genome Atlas - colon adenocarcinoma dataset was used to obtain prognosis-related genes in CRC based on weighted gene co-expression network analysis (WGCNA). A protein-protein interaction network was constructed to screen core targets, with STRING database and Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. Molecular docking was performed with AutoDock Vina software. Core targets were further analyzed using Gene Expression Profiling Interactive Analysis platform, Human Protein Atlas database, University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and GeneMANIA database. In vitro experiments were further performed to investigate the effects of quercetin, one of the main components of CWQ, on CRC cells.</p><p><strong>Results: </strong>6356, 1901 and 2980 CRC-related genes were obtained from differential expression analysis, WGCNA and open access databases, respectively. CWQ contained a total of 70 bioactive ingredients, of which 64 ingredients had a total of 836 therapeutic targets. Functional enrichment analysis indicated that CWQ may be involved in regulating pathways in cancer, MAPK signaling pathway and AGE-RAGE signaling pathway, and further analysis identified 14 core targets of CWQ. These core targets were significantly correlated with cell cycle, p53 signaling pathway, FoxO signaling pathway and pathways in cancer. Among these core targets, cyclin-dependent kinase inhibitor 2 A (CDKN2A) expression was closely associated with shorter overall survival and clinical stage of CRC patients. The main bioactive ingredients of CWQ targeting CDKN2A were quercetin, luteolin, kaempferol, isorhamnetin, 7-O-methylisomucronulatol and 7-Methoxy-2-methyl isoflavone. Additionally, quercetin caused G0/G1 phase arrest and inhibited the viability of CRC cells.</p><p><strong>Conclusion: </strong>The active ingredients of CWQ may play an anti-CRC role through multi-targets and multi-pathways, regulating the cell cycle and cell viability of CRC cells.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"33"},"PeriodicalIF":2.7000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892207/pdf/","citationCount":"0","resultStr":"{\"title\":\"Network pharmacological approach combined with weighted gene co-expression network analysis identifies CDKN2A as the keg target of Changweiqing against colorectal cancer.\",\"authors\":\"Ma Zushuai, Ji Yanrong, Zhao Chengdu, Zhu Xu, Ding Qianshan\",\"doi\":\"10.1186/s41065-025-00405-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Changweiqing (CWQ) is a Chinese herbal formula for the treatment of the gastrointestinal tract diseases, but its role in the treatment of colorectal cancer (CRC) has not been clarified. This study aimed to explore the molecular mechanism of CWQ in CRC treatment through bioinformatics analysis and network pharmacology.</p><p><strong>Methods: </strong>Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction database were used to collect the bioactive components of CWQ. The databases including DisgeNET, GeneCards, MalaCards, Online Mendelian Inheritance in Man and Comparative Toxicogenomics were used to obtain CRC-related targets. The Cancer Genome Atlas - colon adenocarcinoma dataset was used to obtain prognosis-related genes in CRC based on weighted gene co-expression network analysis (WGCNA). A protein-protein interaction network was constructed to screen core targets, with STRING database and Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. Molecular docking was performed with AutoDock Vina software. Core targets were further analyzed using Gene Expression Profiling Interactive Analysis platform, Human Protein Atlas database, University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and GeneMANIA database. In vitro experiments were further performed to investigate the effects of quercetin, one of the main components of CWQ, on CRC cells.</p><p><strong>Results: </strong>6356, 1901 and 2980 CRC-related genes were obtained from differential expression analysis, WGCNA and open access databases, respectively. CWQ contained a total of 70 bioactive ingredients, of which 64 ingredients had a total of 836 therapeutic targets. Functional enrichment analysis indicated that CWQ may be involved in regulating pathways in cancer, MAPK signaling pathway and AGE-RAGE signaling pathway, and further analysis identified 14 core targets of CWQ. These core targets were significantly correlated with cell cycle, p53 signaling pathway, FoxO signaling pathway and pathways in cancer. Among these core targets, cyclin-dependent kinase inhibitor 2 A (CDKN2A) expression was closely associated with shorter overall survival and clinical stage of CRC patients. The main bioactive ingredients of CWQ targeting CDKN2A were quercetin, luteolin, kaempferol, isorhamnetin, 7-O-methylisomucronulatol and 7-Methoxy-2-methyl isoflavone. 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引用次数: 0
摘要
背景与目的:肠味清是一种治疗胃肠道疾病的中草药方剂,但其治疗结直肠癌的作用尚不明确。本研究旨在通过生物信息学分析和网络药理学手段,探讨CWQ治疗结直肠癌的分子机制。方法:采用中药系统药理学数据库及分析平台和SwissTargetPrediction数据库,对中药复方青wq的生物活性成分进行收集。使用DisgeNET、GeneCards、MalaCards、Online Mendelian Inheritance in Man和Comparative Toxicogenomics等数据库获取crc相关靶点。基于加权基因共表达网络分析(WGCNA),使用Cancer Genome Atlas -结肠腺癌数据集获得CRC中预后相关基因。利用STRING数据库和Cytoscape软件构建蛋白-蛋白相互作用网络,筛选核心靶点。使用Database for Annotation、Visualization和Integrated Discovery数据库进行基因本体和京都基因与基因组百科全书的富集分析。用AutoDock Vina软件进行分子对接。使用基因表达谱交互分析平台、人类蛋白图谱数据库、阿拉巴马大学伯明翰分校癌症数据分析门户网站(UALCAN)和GeneMANIA数据库进一步分析核心靶点。体外实验进一步研究槲皮素对结直肠癌细胞的作用,槲皮素是槲皮素的主要成分之一。结果:从差异表达分析、WGCNA和开放获取数据库中分别获得6356、1901和2980个crc相关基因。CWQ共含有70种生物活性成分,其中64种成分共有836个治疗靶点。功能富集分析表明,CWQ可能参与调控癌症通路、MAPK信号通路和AGE-RAGE信号通路,进一步分析确定了CWQ的14个核心靶点。这些核心靶点与细胞周期、p53信号通路、FoxO信号通路及肿瘤通路均有显著相关性。在这些核心靶点中,细胞周期蛋白依赖性激酶抑制剂2a (CDKN2A)的表达与CRC患者较短的总生存期和临床分期密切相关。CWQ靶向CDKN2A的主要生物活性成分为槲皮素、木犀草素、山奈酚、异鼠李素、7- o -甲基异聚脲醇和7-甲氧基-2-甲基异黄酮。此外,槲皮素引起G0/G1期阻滞,抑制结直肠癌细胞的活力。结论:青wq有效成分可能通过多靶点、多途径发挥抗结直肠癌作用,调节结直肠癌细胞的细胞周期和细胞活力。
Network pharmacological approach combined with weighted gene co-expression network analysis identifies CDKN2A as the keg target of Changweiqing against colorectal cancer.
Background and objective: Changweiqing (CWQ) is a Chinese herbal formula for the treatment of the gastrointestinal tract diseases, but its role in the treatment of colorectal cancer (CRC) has not been clarified. This study aimed to explore the molecular mechanism of CWQ in CRC treatment through bioinformatics analysis and network pharmacology.
Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction database were used to collect the bioactive components of CWQ. The databases including DisgeNET, GeneCards, MalaCards, Online Mendelian Inheritance in Man and Comparative Toxicogenomics were used to obtain CRC-related targets. The Cancer Genome Atlas - colon adenocarcinoma dataset was used to obtain prognosis-related genes in CRC based on weighted gene co-expression network analysis (WGCNA). A protein-protein interaction network was constructed to screen core targets, with STRING database and Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. Molecular docking was performed with AutoDock Vina software. Core targets were further analyzed using Gene Expression Profiling Interactive Analysis platform, Human Protein Atlas database, University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and GeneMANIA database. In vitro experiments were further performed to investigate the effects of quercetin, one of the main components of CWQ, on CRC cells.
Results: 6356, 1901 and 2980 CRC-related genes were obtained from differential expression analysis, WGCNA and open access databases, respectively. CWQ contained a total of 70 bioactive ingredients, of which 64 ingredients had a total of 836 therapeutic targets. Functional enrichment analysis indicated that CWQ may be involved in regulating pathways in cancer, MAPK signaling pathway and AGE-RAGE signaling pathway, and further analysis identified 14 core targets of CWQ. These core targets were significantly correlated with cell cycle, p53 signaling pathway, FoxO signaling pathway and pathways in cancer. Among these core targets, cyclin-dependent kinase inhibitor 2 A (CDKN2A) expression was closely associated with shorter overall survival and clinical stage of CRC patients. The main bioactive ingredients of CWQ targeting CDKN2A were quercetin, luteolin, kaempferol, isorhamnetin, 7-O-methylisomucronulatol and 7-Methoxy-2-methyl isoflavone. Additionally, quercetin caused G0/G1 phase arrest and inhibited the viability of CRC cells.
Conclusion: The active ingredients of CWQ may play an anti-CRC role through multi-targets and multi-pathways, regulating the cell cycle and cell viability of CRC cells.
HereditasBiochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍:
For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.