类风湿关节炎患者血浆外泌体微小RNA的差异表达谱

Differential Expression Profiles of Plasma Exosomal microRNAs in Rheumatoid Arthritis.

作者信息

Yang Xiaoke, Wang Zhixin, Zhang Mingming, Shuai Zongwen

机构信息

Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.

出版信息

J Inflamm Res. 2023 Aug 28;16:3687-3698. doi: 10.2147/JIR.S413994. eCollection 2023.

Abstract

AIM

Differential expression maps of microRNAs (miRNAs) are connected to the autoimmune diseases. This study sought to elucidate the expression maps of exosomal miRNA in plasma of rheumatoid arthritis (RA) patients and their potential clinical significance.

METHODS

In the screening phase, small RNA sequencing was performed to characterize dysregulated exosome-derived miRNAs in the plasma samples from six patients with RA and six healthy patients. At the independent verification stage, the candidate plasma exosomal miRNAs were verified in 40 patients with RA and 32 healthy patients by using qRT-PCR. The correlation of miRNA levels and clinical characteristics was tested in patients with RA. The value of these miRNAs in diagnosing RA was assessed with the receiver operating characteristic curve.

RESULTS

During the screening phase, 177 and 129 miRNAs were increased and decreased in RA patients and healthy controls, respectively. There were 10 candidate plasma exosomal miRNAs selected for the next identification. Compared with the healthy controls, eight plasma exosomal miRNAs (let-7a-5p, let-7b-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-128-3p, and miR-25-3p) were significantly elevated in RA patients, but miR-144-3p and miR-15a-5p expression exhibited no significant changes. The let-7a-5p and miR-25-3p levels were linked to the rheumatoid factor-positive phenotype in RA patients. For the eight miRNAs, the area under the subject work characteristic curve (AUC) is 0.641 to 0.843, and their combination had a high diagnostic accuracy for RA (AUC = 0.916).

CONCLUSION

Our study illustrates that novel exosomal miRNAs in the plasma may represent potential noninvasive biomarkers for RA.

摘要

目的

微小RNA(miRNA)的差异表达图谱与自身免疫性疾病相关。本研究旨在阐明类风湿关节炎(RA)患者血浆中外泌体miRNA的表达图谱及其潜在的临床意义。

方法

在筛选阶段,对6例RA患者和6例健康对照者的血浆样本进行小RNA测序,以鉴定失调的外泌体来源的miRNA。在独立验证阶段,通过qRT-PCR在40例RA患者和32例健康对照者中验证候选血浆外泌体miRNA。检测RA患者中miRNA水平与临床特征的相关性。用受试者工作特征曲线评估这些miRNA在诊断RA中的价值。

结果

在筛选阶段,RA患者和健康对照者中分别有177个和129个miRNA表达上调和下调。选择了10个候选血浆外泌体miRNA进行下一步鉴定。与健康对照者相比,RA患者中8种血浆外泌体miRNA(let-7a-5p、let-7b-5p、let-7d-5p、let-7f-5p、let-7g-5p、let-7i-5p、miR-128-3p和miR-25-3p)显著升高,但miR-144-3p和miR-15a-5p表达无显著变化。let-7a-5p和miR-25-3p水平与RA患者类风湿因子阳性表型相关。对于这8种miRNA,受试者工作特征曲线下面积(AUC)为0.641至0.843,它们的组合对RA具有较高的诊断准确性(AUC = 0.916)。

结论

我们的研究表明,血浆中新型外泌体miRNA可能是RA潜在的非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9281/10473432/2ea159007585/JIR-16-3687-g0001.jpg

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