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GAS5、THRIL 和 RMRP lncRNAs 在类风湿关节炎患者的 T 细胞中表达增加。

The expression of GAS5, THRIL, and RMRP lncRNAs is increased in T cells of patients with rheumatoid arthritis.

机构信息

Department of Cell and Molecular Biology, School of Biology, Faculty of Science, College of Science, University of Tehran, Tehran, Iran.

Department of Rheumatology, Alborz University of Medical Science, Karaj, Iran.

出版信息

Clin Rheumatol. 2019 Nov;38(11):3073-3080. doi: 10.1007/s10067-019-04694-z. Epub 2019 Jul 25.

DOI:10.1007/s10067-019-04694-z
PMID:31346885
Abstract

OBJECTIVE

Long non-coding RNAs (lncRNAs) comprise a large and diverse group of non-coding RNAs (ncRNAs) with important regulatory roles in various biological processes, including the immune system regulation. Rheumatoid arthritis (RA) as an autoimmune disease initiates inflammation in the synovial joints. T cells infiltrating into the synovial membrane have an important role in the pathogenesis of RA. The aim of the current investigation was to analyze the expression of four lncRNAs in the T cells from RA patients and healthy controls.

METHODS

In the current study, we investigated the expression of GAS5, RMRP, IFNϒ-AS1, and THRIL lncRNAs in circulating T cells from 20 patients with RA and 18 healthy matched controls by quantitative real-time PCR. T cell isolation was accomplished using the MAC method. We also analyzed the correlation between lncRNA expression and clinical parameters. Also, the mRNA expression levels of IL-17 and TNF-α and the association between lncRNAs and these cytokines were examined.

RESULTS

The results indicate that T cells of RA patients display increased levels of GAS5 (3.31-fold, p = 0.007), RMRP (2.43-fold, p = 0.02), and THRIL (2.14-fold, p = 0.03) lncRNAs compared with those of controls. Furthermore, a positive correlation was found between RMRP expression and disease duration in RA. Receiver operating characteristic (ROC) curve of GAS5, RMRP, and THRIL has a discriminative value in comparing RA patients and controls.

CONCLUSION

The results suggest lncRNAs may be involved in T cell dysfunction in RA. Further studies are required to see whether these lncRNAs have an effect on dysregulation of immune responses in RA disease. Key Points • 70% of non-coding sequences in the human genome are transcribed to RNA. • A growing body of evidence shows the importance of lncRNAs in innate and adaptive immune cell differentiation and functions. • Important recent works suggest a key role of immune cell lncRNAs in autoimmune processes and diseases including RA.

摘要

目的

长链非编码 RNA(lncRNA)是一大类非编码 RNA(ncRNA),在包括免疫系统调节在内的各种生物学过程中具有重要的调节作用。类风湿关节炎(RA)作为一种自身免疫性疾病,会引发滑膜关节炎症。浸润滑膜的 T 细胞在 RA 的发病机制中起着重要作用。本研究的目的是分析 RA 患者和健康对照者 T 细胞中 4 种 lncRNA 的表达。

方法

在本研究中,我们通过定量实时 PCR 检测了 20 例 RA 患者和 18 例健康匹配对照者循环 T 细胞中 GAS5、RMRP、IFNϒ-AS1 和 THRIL lncRNA 的表达。T 细胞分离采用 MAC 法。我们还分析了 lncRNA 表达与临床参数的相关性。此外,还检测了 lncRNA 与这些细胞因子之间的关系。

结果

结果表明,与对照组相比,RA 患者的 T 细胞中 GAS5(3.31 倍,p=0.007)、RMRP(2.43 倍,p=0.02)和 THRIL(2.14 倍,p=0.03)lncRNA 的水平升高。此外,RA 患者中 RMRP 表达与疾病持续时间呈正相关。GAS5、RMRP 和 THRIL 的 ROC 曲线具有区分 RA 患者和对照组的价值。

结论

结果提示 lncRNA 可能参与 RA 中 T 细胞功能障碍。需要进一步研究这些 lncRNA 是否对 RA 疾病中免疫反应的失调有影响。

关键点

  • 人类基因组中 70%的非编码序列转录为 RNA。

  • 越来越多的证据表明 lncRNA 在固有和适应性免疫细胞分化和功能中具有重要作用。

  • 最近的重要研究工作表明,免疫细胞 lncRNA 在包括 RA 在内的自身免疫过程和疾病中起着关键作用。

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