Department of Rheumatology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China.
The Second Department of Internal Medicine, Ningxia Gem Flower Hospital, Yinchuan 750006, Ningxia, China.
Clin Rheumatol. 2024 Aug;43(8):2585-2594. doi: 10.1007/s10067-024-06999-0. Epub 2024 Jun 13.
Circular RNAs (circRNAs) play various roles in the development of many autoimmune diseases. However, their expression profiles and specific function in Sjögren's Syndrome remains largely unknown.
We aimed to investigate circRNAs potential diagnostic value in primary Sjögren's syndrome (pSS) and contribution to the pathogenesis of pSS.
This study included 102 subjects, 51 pSS patients and 51 healthy controls. The concentration of hsa_circ_0045800 was analyzed in peripheral blood mononuclear cells obtained from 51 pSS patients and 51 healthy controls by qRT-PCR. We established a receiver operating characteristic curve (ROC) to assess the biological diagnostic value of hsa_circ_0045800 for pSS. In addition, we analyzed the correlation between hsa_circ_0045800 and disease activity in Sjogren's syndrome. A differential analysis was also conducted on the concentration of hsa_circ_0045800 in patients in pSS patients before and after treatment. We studied the downstream mechanism of hsa_circ_0045800 through bioinformatics analysis and confirmed it using luciferase reporter gene assay.
We confirmed that the concentration of hsa_circ_0045800 was elevated 10.4-fold in peripheral blood mononuclear cells of pSS patients than in healthy controls (p = 0.00). In the pSS active disease group, the concentration of hsa_circ_0045800 is 2.5-fold higher compared to the pSS non-active disease group (p = 0.04). The concentration of hsa_circ_0045800 after treatment was decreased by 80% compared with that before treatment (p = 0.037), suggesting its utility as a potential marker for monitoring treatment efficacy. ROC curve analysis showed that the diagnostic value of hsa_circ_0045800 in pSS patients was significantly higher than that in healthy controls, with an area under the curve of 0.865, a sensitivity of 74%, and a specificity of 92%. The concentration of hsa_circ_0045800 is correlated with various clinical factors: the concentration of hsa_circ_0045800 is positively associated with age (r = 0.328, P = 0.019), oral dryness (r = 0.331, P = 0.017), while it is negatively correlated with HGB (r = -0.435, P = 0.001) and and hypothyroidism (r = -0.318, P = 0.023). Bioinformatics predictions and luciferase assays indicated that hsa_circ_0045800 acts as a molecular sponge for miR-1247-5p, with SMAD2 being a target gene of miR-1247-5p.
Our study results show that hsa_circ_0045800 potentially contributes to the development and progression of pSS via the miR-1247-5p/SMAD2 pathway. Peripheral blood mononuclear cells are directly involved in the pathogenesis of pSS, and the discovery of hsa_circ_0045800 in peripheral blood mononuclear cells highlights its potential as a novel biomarker for disease activity and diagnosis in patients with pSS. Key Points • The concentration of hsa_circ_0045800 was higher in peripheral blood mononuclear cells of pSS patients. • Hsa_circ_0045800 promoted pSS progression through miR-1247-5p-SMAD2 axis. • Hsa_circ_0045800 is a potential biomarker for pSS.
环状 RNA（circRNAs）在许多自身免疫性疾病的发展中发挥着各种作用。然而，它们在干燥综合征（Sjögren's Syndrome，pSS）中的表达谱和特定功能仍知之甚少。
我们旨在探讨 circRNAs 在原发性干燥综合征（pSS）中的潜在诊断价值及其在 pSS 发病机制中的作用。
本研究纳入了 102 名受试者，其中 51 名为 pSS 患者，51 名为健康对照者。通过 qRT-PCR 分析了 51 名 pSS 患者和 51 名健康对照者外周血单个核细胞中的 hsa_circ_0045800 浓度。我们建立了受试者工作特征曲线（ROC）来评估 hsa_circ_0045800 对 pSS 的生物学诊断价值。此外，我们还分析了 hsa_circ_0045800 与干燥综合征疾病活动度之间的相关性。我们还对治疗前后 pSS 患者外周血单个核细胞中 hsa_circ_0045800 的浓度进行了差异分析。我们通过生物信息学分析研究了 hsa_circ_0045800 的下游机制，并通过荧光素酶报告基因检测进行了验证。
我们证实，pSS 患者外周血单个核细胞中的 hsa_circ_0045800 浓度比健康对照组高 10.4 倍（p=0.00）。在 pSS 活动期疾病组中，hsa_circ_0045800 的浓度比 pSS 非活动期疾病组高 2.5 倍（p=0.04）。与治疗前相比，治疗后 hsa_circ_0045800 的浓度降低了 80%（p=0.037），提示其可用作监测治疗效果的潜在标志物。ROC 曲线分析表明，hsa_circ_0045800 在 pSS 患者中的诊断价值明显高于健康对照组，曲线下面积为 0.865，灵敏度为 74%，特异性为 92%。hsa_circ_0045800 的浓度与各种临床因素相关：hsa_circ_0045800 的浓度与年龄（r=0.328，p=0.019）和口腔干燥（r=0.331，p=0.017）呈正相关，与 HGB（r=-0.435，p=0.001）和甲状腺功能减退症（r=-0.318，p=0.023）呈负相关。生物信息学预测和荧光素酶实验表明，hsa_circ_0045800 作为 miR-1247-5p 的分子海绵发挥作用，SMAD2 是 miR-1247-5p 的靶基因。
我们的研究结果表明，hsa_circ_0045800 可能通过 miR-1247-5p/SMAD2 途径促进 pSS 的发生和发展。外周血单个核细胞直接参与 pSS 的发病机制，在外周血单个核细胞中发现 hsa_circ_0045800 突出了其作为 pSS 患者疾病活动度和诊断的新型生物标志物的潜力。
pSS 患者外周血单个核细胞中的 hsa_circ_0045800 浓度较高。
hsa_circ_0045800 通过 miR-1247-5p-SMAD2 轴促进 pSS 进展。
hsa_circ_0045800 是 pSS 的潜在生物标志物。
