Dermatology Department of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.
Department of Pathophysiology, Third Military Medical University, Chongqing 400038, P.R. China.
Mol Med Rep. 2021 Aug;24(2). doi: 10.3892/mmr.2021.12256. Epub 2021 Jun 29.
The role of circular RNAs (circRNAs) in rheumatoid arthritis (RA) remains to be elucidated. To determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) and to identify novel biomarkers for RA and explore their potential effects in RA, the present study conducted high‑throughput RNA sequencing to analyze circRNA expression profiles in PBMCs from 4 RA patients and 3 healthy controls (HCs). Reverse transcription‑quantitative PCR was used to verify the expression of circPTPN22 in 42 RA patients, 44 HCs and 45 systemic lupus erythematosus (SLE) patients. In addition, bioinformatics analysis and Pearson's correlation test were conducted to assess the correlation of the relationships between circPTPN22 and RA progression. A receiver operating characteristic curve was calculated to evaluate the diagnostic value. Multilevel integrated analysis identified 41 upregulated and 30 downregulated circRNAs in RA patients compared with HCs. circPTPN22 was confirmed to be a common differentially expressed gene in RA and SLE compared with HCs. Area under the curve analysis suggested the diagnostic value of circPTPN22 expression to distinguish RA patients from both HCs and SLE patients. In addition, circPTPN22 levels in RA PBMCs were correlated with RA‑IgG, RA‑IgM, RA‑IgA, anti‑cyclic citrullinated peptide (anti‑CCP), rheumatoid factor and C reactive protein levels. A total of four putative microRNAs (miRNAs or miRs), namely, hsa‑miR‑3074‑5p, hsa‑miR‑373‑3p, hsa‑miR‑766‑3p and hsa‑miR‑34c‑5p, were screened to be sponged by circPTPN22 via bioinformatics analysis and then experimentally verified to be upregulated in RA PBMCs compared with controls. The data suggested that circPTPN22 might be a novel biomarker for the diagnosis of RA and participate in RA pathogenesis through a sponge mechanism.
环状 RNA（circRNA）在类风湿关节炎（RA）中的作用尚待阐明。为了确定外周血单个核细胞（PBMC）中 circRNA 的表达情况，寻找 RA 的新型生物标志物，并探讨其在 RA 中的潜在作用，本研究通过高通量 RNA 测序分析了 4 例 RA 患者和 3 例健康对照（HC）PBMC 中的 circRNA 表达谱。采用逆转录-定量 PCR 法检测 42 例 RA 患者、44 例 HC 和 45 例系统性红斑狼疮（SLE）患者中 circPTPN22 的表达情况。此外，还进行了生物信息学分析和 Pearson 相关性检验，以评估 circPTPN22 与 RA 进展之间的相关性。绘制受试者工作特征曲线评估诊断价值。多水平整合分析发现，与 HC 相比，RA 患者中有 41 个上调和 30 个下调的 circRNA。circPTPN22 被证实是 RA 与 HC 相比与 SLE 共有的差异表达基因。曲线下面积分析表明，circPTPN22 表达区分 RA 患者与 HC 和 SLE 患者的诊断价值。此外，RA PBMC 中的 circPTPN22 水平与 RA-IgG、RA-IgM、RA-IgA、抗环瓜氨酸肽（anti-CCP）、类风湿因子和 C 反应蛋白水平相关。通过生物信息学分析筛选出 4 个假定的 microRNA（miRNA 或 miR），即 hsa-miR-3074-5p、hsa-miR-373-3p、hsa-miR-766-3p 和 hsa-miR-34c-5p，作为 circPTPN22 的潜在靶标，通过实验验证其在 RA PBMC 中较对照组上调。这些数据表明，circPTPN22 可能是 RA 诊断的新型生物标志物，并通过海绵机制参与 RA 发病机制。
