摘要
目的筛选与单心室心脏病相关的miRNA及其靶基因,完成miRNA-靶基因调控网络的构建。方法从基因表达数据库(gene expression omnibus,GEO)中获取GSE136547芯片数据,应用R语言进行分析并筛选差异表达的miRNA,应用miRWalk 3.0预测差异表达miRNA的靶基因,并完成GO和KEGG通路分析。使用String在线数据库进行蛋白互作网络(protein protein interaction network,PPI)分析,利用Cytoscape软件进行miRNA-靶基因及PPI调控网络可视化。结果筛选后获得9个差异表达的miRNAs(P<0.05,|log fold change>1|),其中8个上调,1个下调。GO功能富集显示:差异表达miRNAs的靶基因主要参与对DNA损伤检查点、对β淀粉样蛋白的细胞反应、对β淀粉样蛋白的反应、有丝分裂G_(1)期DNA损伤检查点以及G_(1)期DNA损伤检查点等生物学过程。KEGG富集分析发现:靶基因主要参与MAPK信号通路、PI3K-Akt信号通路、人T细胞白血病病毒1感染、人类巨细胞病毒感染以及癌症中的miRNA等重要通路。miRNA-靶基因调控网络中的miRNA包括:hsa-miR-20a-5p、hsa-miR-18a-5p、hsa-miR-18b-5p、hsa-miR-96-5p。通过CytoHubba插件得到10个关键基因分别为MAPK1、CREB1、VEGFA、ESR1、SMAD2、IGF1R、IGF1、IRS1、APP、CRK。结论在单心室心脏病患者的血液中发现9个miRNAs存在差异性表达,它们可能在单心室心脏病的发病过程中发挥重要作用,为单心室心脏病的诊断提供新的思路和依据。
Purpose This study aims to screen of miRNAs and their target genes associated with single ventricle heart disease(SVHD),and to complete a miRNA-target gene regulatory network construction.Methods The microarray datasets GSE136547 were downloaded from the GEO database.Differentially expressed miRNAs(DEM)between SVHD and control samples were obtained by R software,and the target genes of DEM were predicted using miRWalk 3.0.Besides,Gene ntology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis on target genes were performed in R-studio.The protein-protein interaction network was established by using the String database and the miRNA-target gene network was constructed by Cytoscape software.Results A total of 9 DEMs(8 upregulated and 1 downregulated)in GSE136547 dataset were identified between SVHD and control samples according to P<0.05,|log fold change>1|.GO analysis revealed that target genes of DEM were mainly enriched in DNA damage checkpoint,cellular response to amyloid-beta,response to amyloid-beta,mitotic G1 DNA damage checkpoint and G1 DNA damage checkpoint.The mainly enriched pathways in KEGG included MAPK signaling pathway,PI3K-Akt signaling pathway,human T-cell leukemia virus 1 infection,Human cytomegalovirus infection and microRNAs in cancer.In addition,hsa-miR-20a-5p,hsa-miR-18a-5p,hsa-miR-18b-5p and hsa-miR-96-5p were in the miRNA-target gene network.The top 10 hub genes caculated by CytoHubba in the PPI network were MAPK1,CREB1,VEGFA,ESR1 and SMAD2 as well as IGF1R,IGF1,IRS1,APP and CRK.Conclusion 9 miRNAs are found to be differentially expressed in the blood of patients with SVHD.These miRNAs may play an important in the development of SVHD and provide some novel ideas and basis for the diagnosis of SVHD.
作者
王凯
李钟鸣
李岩松
刘先玲
丁胤彰
孙燕
许迪
WANG Kai;LI Zhong-ming;LI Yan-song;LIU Xian-ling;DING Ying-zhang;SUN Yan;XU Di(Department of Cardiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Geriatrics,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2022年第3期289-294,共6页
Chinese Journal of Clinical and Experimental Pathology
基金
国家自然科学基金(81871359)。
