原发免疫性血小板减少症关键基因与通路的筛选及中药研究OACSCDCSTPCD
Screening of key genes and pathway and analytical research of traditional Chinese medicines for primary immune thrombocytopenia based on bioinformatics analysis
目的:应用生物信息学方法初步筛选原发免疫性血小板减少症(ITP)的关键基因并探索其发病机制,进而预测治疗ITP的潜在中药(TCM).方法:基于美国国家生物技术信息中心(NCBI)的基因芯片原始数据集GSE80401,以P<0.05及|logFC|≥1条件筛选差异miRNA的标准进行分析,得到ITP的差异miRNA.采用miRTarBase、miRDB和TargetScan进行miRNA靶基因预测,在Genecards数据库搜索ITP的靶点,将预测的上调靶基因和下调靶基因分别与疾病靶点取交集,在此基础上,将映射的靶基因分别通过String数据库和Cytoscape构建PPI网络,筛选核心的靶基因,对核心靶基因在DAVID和Omicsbean数据库上进行GO和KEGG通路富集分析.将关键基因导入医学本体信息检索数据库(Coremine Medical)分析治疗关键基因的TCM.结果:筛选出符合条件的差异基因 422个,关键基因 17个,包括BCL2L1、CCND1、CD44、CDKN1A、CREB1、GRB2、MAPK1、MAPK8、PIK3R1、CDK2、CAV1、FGF2、IGF1、SMAD2、SMAD4、TLR4和VEGFA,主要涉及蛋白聚糖、FoXO、PI3K-Akt、人T细胞白血病病毒1感染、内分泌抵抗、黏着斑等信号通路.筛选得到包括人参、赤芍、当归、蜂毒、眼镜蛇、补骨脂、地黄、水牛角、火麻仁、菟丝子、五灵脂和金鸡纳皮等在内的具有防治ITP的TCM共12味.TLR4映射的TCM最多,其次是CCND1和VEGFA.在众多的TCM中,人参同时作用于17个靶点,赤芍、当归和蜂毒同时作用于11个靶点,眼镜蛇和补骨脂同时作用于9个和8个靶点,地黄和水牛角同时作用于7个靶点,火麻仁同时作用于4个靶点,菟丝子同时作用于3个靶点,五灵脂同时作用于2个靶点,提示上述药物具有多靶点防治ITP的潜能.结论:基于生信分析初步预测得到ITP的关键致病基因及具有防治作用的TCM,可为相关TCM新药开发提供靶点及研究思路.
Objective:To preliminarily screen the key genes of primary immune thrombocytopenia(ITP)by bioinformatics method and explore the pathogenesis,so as to predict the potential traditional Chinese medicine(TCM)for the treatment of ITP.Methods:Based on the original microarray data set GSE80401 under the National Center for Biotechnology Information(NCBI),the differential miRNA of ITP were obtained by analyzing the adjusted P<0.05 and |logFC|≥1 as the screening criteria for differential miRNA.miRTarBase,miRDB and TargetScan were used to predict miRNA target genes.The target of ITP was searched in Genecards database,and the predicted up-regulated target genes and down-regulated target genes were intersected with disease targets.On this basis,the mapped target genes were respectively constructed into PPI network through String database and Cytoscape to screen core target genes,and the core target genes were enriched and analyzed in DAVID and Omicsbean databases for GO and KEGG pathways.The key genes were imported into the Coremine Medical database to analyze the TCM for the treatment of key genes.Results:Total of 422 differential genes and 17 key genes were finally screened,including BCL2L1,CCND1,CD44,CDKN1A,CREB1,GRB2,MAPK1,MAPK8,PIK3R1,CDK2,CAV1,FGF2,IGF1,SMAD2,SMAD4,TLR4 and VEGFA,mainly involving proteoglycan,FoXO,PI3K-Akt,human T cell leukemia virus 1 infection,endocrine resistance,focal adhesion and other signal pathways.A total of 12 TCM for ITP prevention and treatment,including ginseng,Radix Paeoniae Rubra,Angelica sinensis,bee venom,cobra,Psoralea corylifolia,Rehmannia glutinosa,buffalo horn,hemp seed,dodder seed,Wulingzhi and Jinji NaPi were screened.TLR4 maps the most TCM,followed by CCND1 and VEGFA.Among many TCM,ginseng acts on 17 targets at the same time,Radix Paeoniae Rubra,Angelica sinensis and bee venom act on 11 targets at the same time,cobra and Psoralea corylifolia act on 9 and 8 targets at the same time,Rehmannia glutinosa and buffalo horn act on 7 targets at the same time,hemp seed act on 4 targets at the same time,dodder seed act on 3 targets at the same time,and wulingzhi act on 2 targets at the same time.It is suggested that these drugs had the potential of multi-target prevention and treatment of ITP.Conclusion:The key pathogenic genes of ITP and the TCM with preventive and thera-peutic effects could be preliminarily predicted based on the analysis of genetic information,which can provide targets and research ideas for the development of related TCM.
乌日图那顺;布仁巴图
内蒙古民族大学附属医院,通辽 028000内蒙古民族大学附属医院,通辽 028000
基础医学
原发免疫性血小板减少症关键基因防治中药生信分析人参赤芍
Primary immune thrombocytopeniaKey geneTraditional Chinese medicines for Prevention and treatmentBioin-formatics analysisGinsengRadix Paeoniate Rubra
《中国免疫学杂志》 2023 (12)
2545-2552,8
本文为国家自然科学基金项目(82274210).
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