基于生物信息学分析miR-30d-5p在注意缺陷多动障碍发病机制中的作用

Analysis of the role of miR-30d-5p in the pathogenesis of attention deficit hyperactivity disorder based on bioinformatics

目的采用生物信息学方法分析miR-30d-5p在注意缺陷多动障碍(ADHD)发病机制中的作用。方法通过TargetScan7.2、miRDB和miRTarBase数据库预测miR-30d-5p的靶基因,利用Cytoscape 3.7.1软件中的ClueGO插件对靶基因进行GO和KEGG富集分析,同时通过Cytoscape 3.7.1软件中的STRING插件构建靶蛋白互作(PPI)网络并筛选出核心基因,通过与ADHD gene数据库中已验证的ADHD相关基因对比,分析miR-30d-5p在ADHD中的作用和意义。结果GO富集显示miR-30d-5p靶基因定位到核质、细胞内细胞器、轴突、细胞膜等细胞结构,并在神经系统中广泛参与到神经元发育、分化、神经元发生的调节、神经元投射发育、顺式调控区结合及顺式调控区序列特异性DNA结合等生物过程。KEGG富集显示miR-30d-5p靶基因显著富集在FoxO信号通路、轴突导向、海马长时程增强和神经营养信号通路。NOTCH1、KRAS、SIRT1、MAPK8、SOCS3、NEDD4、SKP2、BDNF、NEDD4L、SOCS1为miR-30d-5p预测靶基因的PPI网络中的核心基因。与ADHD gene数据库对比结果显示miR-30d-5p预测靶基因有33个基因与ADHD相关,且33个基因中含有预测核心基因BDNF。结论miR-30d-5p通过靶向调控BDNF基因参与ADHD发生发展的过程,miR-30d-5p有潜力成为ADHD诊疗相关的靶点。

Objective To explore the role of miR-30d-5p in the pathogenesis of attention deficit hyperactivity disorder(ADHD)using bioinformatics.Methods The target genes of miR-30d-5p were predicted by TargetScan7.2,miRDB and miRTarBase databases.The ClueGO plug-in in Cytoscape 3.7.1 software was used to perform GO and KEGG enrichment analysis on the target genes,and the STRING plug-in constructed a target protein interaction(PPI)network to screen out core genes,which were compared with ADHD related genes verified in the ADHD gene database to analyze the role and significance of miR-30d-5p in ADHD.Results GO enrichment showed that miR-30d-5p target genes were localized to the nucleoplasm,intracellular organelles,axons,cell membranes and other cell structures,and were widely involved in neuronal development,differentiation,regulation of neuronal development,metaprojection development,cis-regulatory region binding,and cis-regulatory region sequence-specific DNA binding.KEGG enrichment showed that miR-30d-5p target genes were significantly enriched in FoxO signaling pathway,axon guidance,long-term enhancement of hippocampus and neurotrophic signaling pathway.NOTCH1,KRAS,SIRT1,MAPK8,SOCS3,NEDD4,SKP2,BDNF,NEDD4L,SOCS1 were the core genes in the PPI network of miR-30d-5p predicting target genes.Comparison with the ADHD gene database showed that miR-30d-5p predicted that 33 genes of the target genes were related to ADHD,and 33 genes contained the predicted core gene BDNF.Conclusion miR-30d-5p participates in the process of ADHD development by targeting and regulating the BDNF gene.miR-30d-5p has the potential to become a target for the diagnosis and treatment of ADHD.