MicroRNA在胶原诱导型关节炎大鼠中的异常表达及功能分析

Expression and function analysis of microRNA in collagen-induced arthritis rats

目的:类风湿关节炎是一种常见的自身免疫性疾病,微RNA(microRNA,miRNA)可能参与其发病过程。本研究旨在检测胶原诱导型关节炎(collagen-induced arthritis,CIA)大鼠中异常表达的miRNA,并对其靶基因进行生物学功能及通路的富集分析。方法:提取实验动物滑膜内总RNA,通过miRNA芯片获得miRNA基因谱,筛选差异表达miRNA并预测其相关靶基因;对差异表达显著的miRNA靶基因进行基因本体(Gene Ontology,GO)和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果:CIA大鼠模型中有包括rno-miR-6215、rno-miR-709等在内的69个呈显著差异表达的miRNA,其中22个(31.9%)上调和47个(68.1%)下调;GO及KEGG富集分析结果发现上调miRNA的靶基因主要富集于细胞代谢过程,它们可能参与了MAPK和Wnt等信号通路;下调miRNA的靶基因主要富集于神经系统发育,它们可能参与了轴突引导的信号通路。结论:CIA大鼠模型内miRNA呈显著的差异表达,其靶基因可能参与细胞代谢的生物功能及MAPK和Wnt等信号通路。

Objective:Rheumatoid arthritis is a common autoimmune disease,and microRNAs(miRNAs)are involved in its pathogenesis.This study aims to examine the differentially expressed miRNAs in collagen-induced arthritis(CIA)rats,to analyze the biological functions and the related pathways of the miRNA target genes.Methods:The total RNA in the synovium of experimental animals was extracted.The miRNA gene profile was obtained by miRNA microarray.Then the differentially expressed miRNAs were screened and the relevant target mRNAs were predicted.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed on the significantly differentially expressed miRNAs.Results:There were 69 differentially expressed miRNAs including rno-miR-6215 and rnomiR-709 in CIA rats,of which 22(31.9%)were up-regulated and 47(68.1%)were downregulated.GO and KEGG enrichment analysis showed that the up-regulated miRNA target genes were mainly enriched in cellular metabolism,and they were involved in MAPK and Wnt signaling pathways.The down-regulated miRNA target genes were mainly enriched in nervous system development,and they were involved in axon guidance signaling pathway.Conclusion:There are differentially expressed miRNAs in the CIA rat model,which may be involved in metabolism biological functions and signal pathways such as MAPK and Wnt.