大柴胡汤治疗肝细胞癌lncRNA-miRNA-mRNA转录网络整合分析

Integration Analysis of lncRNA-miRNA-mRNA Transcriptional Network in the Treatment of Hepatocellular Carcinoma with Dachaihu Decoction

目的挖掘大柴胡汤治疗肝细胞癌的lncRNA-miRNA-mRNA调控网络,探讨其抗肝癌作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)、GEO、miRDB、miRTarBase、TargetScan数据库获取大柴胡汤的活性成分、预测靶点及肝细胞癌的差异表达长链非编码RNA(lncRNAs)、微小RNA(miRNAs)和mRNAs,通过R语言和Perl软件筛选大柴胡汤治疗肝细胞癌的关键lncRNAs、miRNAs、mRNAs。采用Cytoscape3.7.0软件和STRING数据库构建活性成分-靶点网络、lncRNA-miRNA-mRNA转录网络和蛋白相互作用网络,进行GO和KEGG富集分析,并予分子对接验证,进行整合分析。结果得到大柴胡汤治疗肝细胞癌的97个有效成分和42个靶点,构建了由19个关键lncRNAs、23个关键miRNAs和42个关键mRNAs组成的lncRNA-miRNA-mRNA转录网络。富集分析结果显示,这些靶基因参与了肿瘤的生存、凋亡、自噬、氧化应激、蛋白激酶等生物学过程,主要通过PI3K-Akt信号通路、MAPK信号通路和TNF信号通路等发挥作用。结论大柴胡汤治疗肝细胞癌具有多成分、多靶点、多途径协同作用特点,可为相关研究提供依据和方向。

Objective To characterize the lncRNA-miRNA-mRNA regulatory network of Dachaihu Decoction in the treatment of hepatocellular carcinoma(HCC);To explore its anti-liver cancer mechanism.Methods The active components of Dachaihu Decoction and predicted targets,as well as the differentially expressed lncRNAs,miRNAs,and miRNAs of HCC were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),GEO,miRDB,miRTarBase and TargetScan databases.Furthermore,R language and Perl software were chosen to screen the key lncRNAs,miRNAs and mRNAs for Dachaihu Decoction for the treatment of HCC.With the help of Cytoscape 3.7.0 software and STRING database,the active components-target network,lncRNA-miRNA-mRNA regulatory network and protein-protein interaction network were built.GO and KEGG enrichment analysis were performed,and combined with molecular docking to construct integrated analysis.Results A total of 97 active components and 42 targets were obtained in Dachaihu Decoction for the treatment of HCC,and a lncRNA-mRNA-miRNA regulatory network composed of 19 key lncRNAs,23 key miRNAs,and 42 key mRNAs was built.Enrichment analysis showed that these important target genes were involved in tumor survival,apoptosis,autophagy,oxidative stress,protein kinases and other biological processes,and mainly played a therapeutic role through PI3K-Akt signaling pathway,MAPK signaling pathway and TNF signaling pathway.Conclusion This study indicates the characteristics of Dachaihu Decoction treatment of HCC with multi-components,multi-targets,and multi-pathways synergistic therapy,and can provide basis and direction for future research.