Department of Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang Medical School of Nanjing Medical University, Zhenjiang, China.
Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Front Immunol. 2022 May 24;13:885896. doi: 10.3389/fimmu.2022.885896. eCollection 2022.
Circular RNAs (circRNAs) are important transcriptional regulators of genome expression that participate in the pathogenesis of human diseases. Mechanistically, circRNAs, as competitive endogenous RNAs (ceRNAs), can sponge microRNAs (miRNAs) with miRNA response elements. A previous study identified that hsa_circ_0089172 (circNUP214) is abnormally expressed in Hashimoto's thyroiditis. However, the role of circNUP214 in rheumatoid arthritis (RA) remains unclear. In total, 28 RA patients and 28 healthy controls were enrolled in this study. We found that circNUP214 is an abundant and stable circRNA in RA patients that can potentially differentiate RA patients from healthy subjects. Additionally, the elevated levels of IL-23R positively correlated with circNUP214 expression. The knockdown of circNUP214 resulted in the reduction of IL-23R at both transcriptional and translational levels in human CD4 T cells. The proportion of circulating Th17 cells and the transcript levels of IL-17A were increased in RA patients and were both positively correlated with IL-23R expression. Moreover, positive correlations between the transcript levels of circNUP214 and the percentage of Th17 cells and the transcript levels of IL-17A were observed in RA patients. The downregulation of circNUP214 decreased the proportion of Th17 cells and the transcript levels of IL-17A . Furthermore, circNUP214 functioned as a ceRNA for miR-125a-3p in RA patients. Taken together, our results indicate that elevated levels of circNUP214 contribute to the Th17 cell response in RA patients.
环状 RNA（circRNAs）是重要的基因组表达转录调控因子，参与人类疾病的发病机制。从机制上讲，环状 RNA 作为竞争性内源性 RNA（ceRNA），可以与具有 miRNA 反应元件的 miRNA 结合。先前的研究表明，hsa_circ_0089172（circNUP214）在桥本甲状腺炎中异常表达。然而，circNUP214 在类风湿关节炎（RA）中的作用尚不清楚。本研究共纳入 28 例 RA 患者和 28 例健康对照者。我们发现，circNUP214 是 RA 患者中一种丰富且稳定的环状 RNA，可潜在地区分 RA 患者和健康受试者。此外，IL-23R 的上调水平与 circNUP214 的表达呈正相关。在人 CD4 T 细胞中，circNUP214 的敲低导致 IL-23R 在转录和翻译水平上的降低。RA 患者外周血中 Th17 细胞的比例和 IL-17A 的转录水平升高，均与 IL-23R 的表达呈正相关。此外，在 RA 患者中观察到 circNUP214 的转录水平与 Th17 细胞的比例和 IL-17A 的转录水平之间存在正相关。circNUP214 的下调降低了 Th17 细胞的比例和 IL-17A 的转录水平。此外，circNUP214 在 RA 患者中作为 miR-125a-3p 的 ceRNA 发挥作用。综上所述，我们的研究结果表明，circNUP214 的高水平促进了 RA 患者 Th17 细胞的反应。
