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长链非编码RNA分析揭示了类风湿性关节炎患者外周血单核细胞中与疾病活动相关的差异表达长链非编码RNA。

Long noncoding RNA profiling revealed differentially expressed lncRNAs associated with disease activity in PBMCs from patients with rheumatoid arthritis.

作者信息

Yuan Min, Wang Shujun, Yu Lijie, Qu Bo, Xu Liming, Liu Lining, Sun Huanxia, Li Chunxian, Shi Yanjun, Liu Huaxiang

机构信息

Department of Rheumatology, Shandong University Qilu Hospital, Jinan, China.

Department of Rheumatology, Liaocheng People's Hospital, Liaocheng, China.

出版信息

PLoS One. 2017 Nov 15;12(11):e0186795. doi: 10.1371/journal.pone.0186795. eCollection 2017.

Abstract

Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators, and the aberrant expression of lncRNAs has been reported in numerous diseases. However, the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) has not been well documented. We applied a microarray analysis to profile the lncRNA and mRNA expression in 3 pairs of samples. Each sample was mixed with equivalent PBMCs from 9 female RA patients and 9 corresponding healthy controls, and the data were validated via qPCR using another cohort that comprised 36 RA patients and 24 healthy controls. A bioinformatic analysis was performed to investigate the potential functions of differentially expressed genes. Overall, 2,099 lncRNAs and 2,307 mRNAs were differentially expressed between the RA patients and healthy controls. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of RA through several different pathways. The qPCR results showed that the expression levels of ENST00000456270 and NR_002838 were significantly increased in the RA patients, whereas the expression levels of NR_026812 and uc001zwf.1 were significantly decreased. Furthermore, the expression level of ENST00000456270 was strongly associated with the serum levels of IL-6 and TNF-a and the Simplified Disease Activity Index (SDAI) of the RA patients. Our data provided comprehensive evidence regarding the differential expression of lncRNAs in PBMCs of RA patients, which shed light on the understanding of the molecular mechanisms of lncRNAs in the pathogenesis of RA.

摘要

长链非编码RNA(lncRNAs)最近已成为重要的生物调节因子,并且lncRNAs的异常表达已在多种疾病中被报道。然而,lncRNAs在类风湿性关节炎(RA)患者外周血单个核细胞(PBMCs)中的表达尚未得到充分记录。我们应用微阵列分析来描绘3对样本中lncRNA和mRNA的表达情况。每个样本均与来自9名女性RA患者和9名相应健康对照的等量PBMCs混合,并使用另一个由36名RA患者和24名健康对照组成的队列通过qPCR对数据进行验证。进行了生物信息学分析以研究差异表达基因的潜在功能。总体而言,RA患者和健康对照之间有2099个lncRNAs和2307个mRNAs差异表达。生物信息学分析表明,差异表达的lncRNAs调节异常表达的mRNAs,这些mRNAs通过几种不同途径参与RA的发病机制。qPCR结果显示,RA患者中ENST00000456270和NR_002838的表达水平显著升高,而NR_026812和uc001zwf.1的表达水平显著降低。此外,ENST00000456270的表达水平与RA患者的血清IL-6和TNF-α水平以及简化疾病活动指数(SDAI)密切相关。我们的数据提供了关于RA患者PBMCs中lncRNAs差异表达的全面证据,这有助于深入了解lncRNAs在RA发病机制中的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f01/5687725/ce1d2f97a661/pone.0186795.g001.jpg

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