摘要
Background:Patients diagnosed with ulcerative colitis(UC)are known to have an increased susceptibility to colorectal cancer(CRC).However,the shared underlying mechanisms between UC and CRC remain unclear.Given the therapeutic potential of luteolin in both UC and CRC,this study aims to elucidate the molecular targets and mechanisms through which luteolin exerts its effects against these diseases.Methods:The GeneCards database,DisGENet database,and Gene Expression Omnibus database were utilized to analyze the targets associated with UC and CRC.Subsequently,the Traditional Chinese Medicine Systems Pharmacology and SwissTargetPrediction databases were employed to identify luteolin-related targets.The identified luteolin-related targets were then mapped to official gene symbols using the UniProt database.The Cytoscape 3.9.0 software was utilized to construct a network of luteolin-associated targets.Venn diagram analysis was performed to identify common targets among UC,CRC,and luteolin.The common targets were further analyzed using the STRING database to construct a protein-protein interaction network.The“cytoHubba”plugin in Cytoscape 3.9.0 was employed to identify hub targets within the PPI network.Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on the hub targets.Finally,molecular docking using AutoDock and PyMOL software was performed to assess the binding affinity between luteolin and the hub targets.Results:Luteolin was found to interact with a total of 149 pharmacological targets,while UC and CRC were associated with 1232 and 3278 targets,respectively.Forty-six common targets were identified among luteolin,UC,and CRC.Through the application of seven different algorithms,seven hub targets were identified,TP53,AKT1,TNF,SRC,EGFR,and MMP9.Bioinformatics enrichment analysis revealed 49 enriched pathways through Kyoto Encyclopedia of Genes and Genomes analysis,while Gene Ontology analysis yielded a total of 245 biological processes,4 cellular components,and 7 molecular functions.Molecular docking simulations demonstrated a good binding affinity between luteolin and the hub targets.Conclusion:This study identified multiple potential pharmacological targets and elucidated various biological pathways through which luteolin may exert its therapeutic effects in the treatment of UC and CRC.These findings provide a solid theoretical foundation for further experimental investigations in the treatment of UC and CRC.
基金
supported by the Key Research and Development Program of Shaanxi Province(2020ZDLSF05-02)
the Key Science and Technology Project of New Agricultural Variety Breeding of Zhejiang Province(2021C02074).
