目的:应用生物信息学技术探索肾移植术后抗体介导排斥反应(antibody-mediated rejec-tion，AMR)的差异表达基因，筛选出miRNA参与肾移植术后AMR的可能发生机制及潜在治疗靶点，以期为移植后AMR靶向治疗提供新思路。方法:从基因表达数据库(GEO)中下载数据集GSE115816，使用DESeq2R包在线分析肾移植术后移植肾功能稳定(SGF)组和AMR组的差异表达miRNAs，Targetscan软件预测miRNA的相关作用靶点，差异性表达基因(DEGs)进行基因本体(gene ontology，GO)分析、京都基因与基因组百科全书(Kyoto encyclopedia of genes and ge-nomes，KEGG)通路富集分析;利用String数据库cytohubba进行关键基因(Hub基因)筛选，最后TargetScan在线分析进行验证。结果:与SGF组相比，AMR组共发现10个差异性表达的miRNA，其中miR-144-5p的表达差异最具有显著性。使用Targetscan软件预测miR-144-5p的相关作用靶点，共143个。GO分析表明，DEGs主要参与血管生成、突触信号传递、转录共激活因子调控。KEGG通路富集分析表明，DEGs主要富集于甲状腺激素信号通路、人类乳头瘤病毒感染、PI3K-AKT信号通路。蛋白质-蛋白质相互作用(PPI)网络筛选出10个Hug基因。基于cytoHubba中的6种算法，取各个算法的前10个Hug基因取交集后得到5个关键基因，分别是 NCOA2、NCOA1、FOXO1、PAX3、PPARGC1A。经过文献调研发现FoxO1在免疫系统疾病及肾脏疾病中发挥重要作用，本研究选择FoxO1作为miR-144-5P的潜在作用靶点蛋白。最终，TargetScan在线分析结果显示，miR-144-5p与FoxO1的3'UTR区有靶向结合的位点。结论:miR-144-5p是参与肾移植术后AMR的关键miRNA，miR-144-5p靶向FoxO1可能作为AMR的潜在治疗靶点及预后生物标志物。
The bioinformatics analysis of miR-144-5p regulated FoxO1 as a po-tential therapeutic target for antibody-mediated rejection in kidney transplantation
AIM:In this study,bioinformatics tech-nology was used to explore the differentially ex-pressed genes in antibody-mediated rejection after renal transplantation,and to screen out the possi-ble mechanisms and potential therapeutic targets of AMR-related miRNAs after renal transplantation,in order to provide new idea for the targeted thera-py of AMR after transplantation.METHODS:The dataset GSE115816 was downloaded from the GEO database,and the differential expression of miR-NAs in stable renal transplantation(SGF)group and the antibody-mediated rejection(AMR)group after renal transplantation was analyzed online by using DESeq 2R software.TargetScan software predicted the related targets of miRNAs,and the differential-ly expressed genes(DEGs)were analyzed through through gene ontology(GO)enrichment analysis and Kyoto gene and genome encyclopedia(KEGG)enrichment analysis,then key genes were screened by String database and Cytoscape,and finally veri-fied by TargetScan online analysis.RESULTS:A total of 10 differentially expressed miRNAs were identi-fied in the AMR group by comparison with the SGF group,with the most significant difference in ex-pression of miR-144-5p.A total of 143 miR-144-5p related targets were predicted by Targetscan soft-ware.GO analysis showed that DEGs were mainly involved in angiogenesis,synaptic signaling,and transcriptional co-activator regulation.KEGG analy-sis showed that DEGs were mainly enriched in the thyroid hormone signaling pathway,human papillo-mavirus infection,and PI3K-AKT signaling pathway.The 10 Hug genes were screened by PPI network.Based on the 6 algorithms in cytoHubba,5 key genes were obtained by taking the intersection of the top 10 Hug genes of each algorithm,which were NCOA2,NCOA1,FOXO1,PAX3,and PPARGC1A.After the literature review,we found that FoxO1 plays an essential role in immune sys-tem diseases and kidney diseases.In our study,we chose FoxO1 as a potential target protein for miR-144-5p.Finally,TargetScan online analysis showed that miR-144-5p has a targeted binding site with the 3'UTR region of FoxO1.CONCLUSION:MiR-144-5p plays an important role in AMR after Kidney transplantation.MiR-144-5p targeting FoxO1 may be a potential therapeutic target and prognostic biomarker for AMR.
万方数据
维普
