类风湿关节炎外周血lncRNA差异表达研究

摘要

目的：筛选长链非编码RNA（ lncRNA）在类风湿性关节炎患者PBMCs和正常人PBMCs中差异表达，分析lncRNA在RA发病中的可能作用。方法：选取2014年湖北民族学院附属民大医院风湿免疫科就诊的12例RA患者和11例正常对照组。利用Agilent human lncRNA芯片检测3例RA患者PBMCs和3例正常人PBMCs中lncRNA和mRNA表达，GO及Pathway分析差异表达的lncRNA功能分布，构建lncRNA－mRNA的共表达网络，并在此基础上通过Cis－和Trans－预测可能与RA相关lncRNA。结果：RA患者中差异表达的lncRNA共有1615条，差异表达的mRNA共有878条，GO分析发现差异表达的mRNA主要参与金属离子结合、蛋白激酶结合、转录调节及核苷酸结合等。 Pathway分析发现差异表达的mRNA主要参与TNF信号通路、B细胞受体信号通路、前列腺癌、系统性红斑狼疮、子宫内膜癌等。经Cis－和Trans－预测发现，REL、SMAD3和ETS1可能与RA的发生密切相关，因此考虑与之相关的lncRNA：NONHSAG027875、FR378506和NONHSAT031501也可能参与了RA的发生。结论：RA患者外周血中差异表达的lncRNA可能与RA的发生和发展密切相关，未来可能成为RA潜在治疗靶点。%Objective:To investigate the expression profile variation of long non-coding RNA( lncRNA) in the peripheral blood mononuclear cells of rheumatoid arthritis ( RA ) and healthy controls, and explore the role of lncRNA in the pathogenesis of RA.Methods:A total of 12 RA patients and 11 age-matched healthy controls from University Hospital of Hubei University for Nationalities were recruited.Using lncRNA microarray technology to detect differently expressed lncRNAs in 3 cases of RA PBMCs and 3 cases of healthy controls.GO and Pathway analysis was performed.The coding-non-coding gene co-expression networks of lncRNA and mRNA was constructed based on the correlation analysis,and then searched lncRNA in pathogenesis of RA through the cis-analysis and trans-analysis.Results:A total of 1 615 deregulated lncRNAs and 878 deregulated mRNAs were detected in RA patients.GO analysis of different expressed mRNA may involve in metal ion binding,protein kinase binding,nucleotide binding,regulation of transcription,et al.Pathway analysis of different expressed mRNA may involve in TNF signaling pathway,B cell receptor signaling pathway,pancreatic cancer,system lupus erythematosus endometrial cancer,et al.REL,SMAD3 and ETS1 may play an important role in the pathogenesis and development of RA through cis-analysis and trans-analysis.As the NONHSAG027875,FR378506 and NONHSAT031501 also had the similar function,and they may be related to the pathogenesis and development of RA.Conclusion:Differentially expressed lncRNAs may exert a partial role in RA,and may provide potential targets for future treatment of RA.