基于生物信息学构建带状疱疹神经痛miRNA-mRNA调控网络

Construction of a miRNA-mRNA regulatory network for zoster-associated neuralgia based on bioinformatics

目的:利用生物信息学的方法构建带状疱疹相关神经痛miRNA-mRNA调控网络。方法:从GEO数据库获取水痘-带状疱疹病毒感染的神经母细胞瘤细胞(SH-SY5Y)转录组测序数据。利用R软件整合差异表达基因。通过miRNet数据库和FunRich软件筛选疼痛相关miRNAs和下游靶基因,并与整合的差异表达基因取交集,获得miRNA-mRNA关系对,且对网络中miRNAs和靶基因分别进行上游转录因子预测和GO、KEGG分析。通过String数据库建立蛋白质互作网络,并利用Cytoscape软件筛选Hub基因。结果:共筛选到差异表达基因1250个、靶基因123个,GO富集分析发现其主要与轴突生成、中枢神经系统神经元发育、电压门控钠通道活性、转录辅助因子结合等生物过程和分子功能相关。KEGG富集分析发现其主要参与轴突引导、昼夜节律、神经活性配体-受体相互作用等信号通路。结论:成功构建了带状疱疹神经痛miRNA-mRNA调控网络,并筛选得到了mir-34c、mir-98、mir-183、mir-107和SLIT2、ROBO2、ROBO1、PER2、F2RL2、GRID2、S1PR1等关键mi RNA和靶基因,为进一步挖掘其分子发病机制提供了理论基础。

Objective:To construct a miRNA-mRNA regulatory network for zoster-associated neuralgia using a bioinformatics approach.Methods:The transcriptome sequencing data of varicella-zoster virus-infected neuroblastoma cells(SH-SY5Y)were obtained from the GEO database.The differentially expressed genes were integrated by R software.Pain-related miRNAs and the downstream target genes were screened by miRNet database and FunRich software and intersected with the integrated differentially expressed genes to obtain miRNA-mRNA relationship pairs.Upstream transcription factor prediction,GO and KEGG analysis were performed for miRNAs and target genes in the network,respectively.The String online database was accessed to develop the protein interaction network and the Hub genes were screened using Cytoscape software.Results:A total of 1250 differentially expressed genes and 123 target genes were screened.GO analysis showed that they were mainly related to biological processes and molecular functions such as axon genesis,central nervous system neuron development,voltage-gated channel activity,and transcription cofactor binding.KEGG analysis showed that they were mainly involved in axon guidance,circadian rhythm,and neuroactive ligand-receptor interaction.Conclusion:We successfully constructed a miRNA-mRNA regulatory network for zoster-associated neuralgia and obtained key miRNAs and target genes such as mir-34c,mir-98,mir-183,mir-107 and SLIT2,ROBO2,ROBO1,PER2,F2RL2,GRID2,S1PR1,which provide a theoretical basis for further exploration of its molecular pathogenesis.