miR-27a在原发性痛风关节炎患者中的表达水平及生物信息学分析

MiR-27a expression and bioinformatics analysis of its predicted target genes in primary gouty arthritis

目的 检测miR-27a在原发性痛风性关节炎(PGA)患者的表达水平,运用生物信息学方法研究miR-27a及其靶基因在PGA发生、发展过程中的作用。方法 采用实时荧光定量PCR检测miR-27a在PGA患者外周血单个核细胞中的表达水平,应用UCSC基因组在线软件分析miR-27a在不同物种间的保守性,采用TargetScan、miRDB和RNA22数据库进行靶基因预测,并结合GeneCards数据库,对痛风相关的靶基因进行GO富集分析和KEGG信号通路分析。结果 miR-27a在PGA患者中表达明显降低,其核苷酸序列在多物种间呈高度保守性。受miR-27a调控,且与PGA疾病相关的潜在靶基因包括MAPK14、RFX3、ABCA1、HS2ST1、ENPEP和CACNA2D3等。GO富集分析发现,miR-27a的靶基因参与细胞代谢调节及对外界刺激的反应等多种生物学功能。KEGG信号通路分析发现,miR-27a的靶基因显著富集在MAPK信号通路、细胞因子-细胞因子受体相互作用、糖尿病通路和醛固酮控制的钠盐重吸收通路等。结论 miR-27a可能通过调控多个与痛风发病相关的靶基因,参与多条信号通路的调节,从而参与痛风炎症免疫反应机制。

Objective To detect expression level of miR-27 a in patients with primary gouty arthritis(PGA),and to explore the role of miR-27 a and its target genes by bioinformatics analysis.Methods Expression level of miR-27 a in peripheral blood mononuclear cells of PGA patients was detected by quantitative RT-PCR.UCSC genome browser was used to analyze the conservation of miR-27 a among different species.Combining with the gout related genes of GeneCards,TargetScan,miRDB and RNA22 database were used to predict the intersection target genes of miR-27 a.Then GO enrichment and KEGG signal pathway enrichment of miR-27 a target genes were further analyzed.Results MiR-27 a expression was significantly reduced in PGA patients,and its sequence was conserved highly among species.These target genes were predicted to be regulated by miR-27 a and associated with gout,including MAPK14,RFX3,ABCA1,HS2 ST1,ENPEP,CACNA2 D3 and other genes.GO enrichment analysis revealed that the target genes of miR-27 a were involved in a variety of biological functions such as cell metabolic regulation and response to external stimuli.KEGG signal pathway analysis showed that the target genes of miR-27 a were significantly enriched in a series of signaling pathways including MAPK signaling pathway,cytokine-cytokine receptor interaction,diabetes pathway and aldosterone-regulated sodium reabsorption pathway.Conclusion MiR-27 a maybe directly regulate its target molecules associated with gouty arthritis,mediate various signal pathway networks,thus participate in mechanism of inflammatory immune response in gouty arthritis.