Department of Orthopaedic Sports Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, South Baixiang, Ouhai District, Wenzhou, 325000, China.
Clin Rheumatol. 2019 Jun;38(6):1753-1765. doi: 10.1007/s10067-018-04417-w. Epub 2019 Feb 1.
This study aimed to investigate microRNA (miRNA) expression profiles in synovium tissues of rheumatoid arthritis (RA) patients by RNA sequencing and to evaluate the values of dysregulated miRNAs in RA diagnosis and monitoring.
Thirty RA patients who underwent knee arthroscopy and 30 controls with knee trauma who underwent surgery were consecutively recruited, and synovium tissue samples of both groups were obtained during surgeries. In the exploration part, miRNA and mRNA expression profiles of 3 RA samples and 3 control samples were detected using RNA sequencing then followed by bioinformatic analyses. In the validation part, 5 candidate miRNA levels were detected by quantitative polymerase chain reaction (qPCR) in 30 RA patients and 30 control patients.
In the exploration part, 78 miRNAs and 1582 mRNAs were upregulated while 40 miRNAs and 1295 mRNAs were downregulated in synovium tissue samples of RA patients compared with those of controls. Furthermore, enrichment analyses revealed that these dysregulated miRNAs and mRNAs were mainly implicated in immune activities and inflammatory diseases such as leukocyte migration, complement activation, and RA. In the validation part, qPCR assay revealed that miR-5571-3p and miR-135b-5p expressions were increased in RA patients compared with those in controls and disclosed good predictive values for RA risk with high area under the curves (AUCs). Besides, both miR-5571-3p and miR-135b-5p levels were positively correlated with disease activity and inflammation level of RA.
Analyses of miRNA expression profiles by sequencing indicate that miR-5571-3p and miR-135b-5p correlate with increased RA risk and activity.
本研究旨在通过 RNA 测序分析类风湿关节炎(RA)患者滑膜组织中的 microRNA(miRNA)表达谱,并评估失调 miRNA 在 RA 诊断和监测中的价值。
连续纳入 30 例接受膝关节镜检查的 RA 患者和 30 例因膝关节创伤接受手术的对照者,并在手术期间获取两组的滑膜组织样本。在探索部分,使用 RNA 测序检测 3 例 RA 样本和 3 例对照样本的 miRNA 和 mRNA 表达谱,然后进行生物信息学分析。在验证部分,通过定量聚合酶链反应(qPCR)检测 30 例 RA 患者和 30 例对照患者的 5 个候选 miRNA 水平。
在探索部分,与对照组相比,RA 患者滑膜组织中 78 个 miRNA 上调,1582 个 mRNA 上调,40 个 miRNA 下调,1295 个 mRNA 下调。此外,富集分析显示,这些失调的 miRNA 和 mRNA 主要参与免疫活性和炎症性疾病,如白细胞迁移、补体激活和 RA。在验证部分,qPCR 检测显示,miR-5571-3p 和 miR-135b-5p 在 RA 患者中的表达高于对照组,具有较高的曲线下面积(AUC),对 RA 风险具有良好的预测价值。此外,miR-5571-3p 和 miR-135b-5p 水平与 RA 的疾病活动度和炎症水平呈正相关。
通过测序分析 miRNA 表达谱表明,miR-5571-3p 和 miR-135b-5p 与 RA 风险增加和活性相关。