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已发表论文
揭示类风湿关节炎中的环状 RNA 特征：新型生物标志物及临床意义
Authors Yang X, Yang Z, Zhang M, Xu S, Shuai Z
Received 20 June 2025
Accepted for publication 23 November 2025
Published 16 December 2025 Volume 2025:18 Pages 17651—17662
DOI https://doi.org/10.2147/JIR.S548400
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Ujjwol Risal
Xiaoke Yang,* Zhongling Yang,* Mingming Zhang, Shengqian Xu, Zongwen Shuai
Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zongwen Shuai, Email shuaizongwen@ahmu.edu.cn
Background: Although increasing evidence implicates circular RNAs (circRNAs) in the pathogenesis of various autoimmune diseases, the potential role of circRNAs in rheumatoid arthritis (RA) remains poorly understood.
Methods: Utilizing a two-phase study design, we performed high-throughput RNA sequencing on peripheral blood mononuclear cells (PBMCs) from three treatment-naïve RA patients and three healthy controls (HCs), followed by validation in an independent cohort of 32 RA patients and 32 HCs using real-time quantitative polymerase chain reaction (RT-qPCR).
Results: A total of 157 circRNAs were differentially expressed between RA patients and HCs, including 91 upregulated and 66 downregulated circRNAs. Six circRNAs, including hsa_circ_0001394, hsa_circ_0001998, hsa_circ_0009172, hsa_circ_0006732, circRNA2842, and circRNA8330, were further confirmed to be upregulated in RA. Among them, hsa_circ_0001394 demonstrated perfect sensitivity (100%), and hsa_circ_0001998 exhibited perfect specificity (100%) in distinguishing RA from HCs. All six circRNAs showed considerable diagnostic performance, with area under the curve (AUC) values ranging from 0.794 to 0.993. Additionally, specific circRNAs correlated significantly with established serological markers: hsa_circ_0009172 expression was negatively associated with anti-cyclic citrullinated peptide (anti-CCP) antibody titers, whereas hsa_circ_0001998 expression correlated positively with rheumatoid factor (RF). Pathway enrichment analysis suggested that these differentially expressed circRNAs may participate in RA pathogenesis through key pathways like Wnt, calcium and VEGF signaling.
Conclusion: Our study identifies several novel circRNAs with high diagnostic utility for RA, highlighting their potential as promising biomarkers and therapeutic targets.
Keywords: rheumatoid arthritis, circular RNAs, PBMCs, biomarker
Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zongwen Shuai, Email shuaizongwen@ahmu.edu.cn
Background: Although increasing evidence implicates circular RNAs (circRNAs) in the pathogenesis of various autoimmune diseases, the potential role of circRNAs in rheumatoid arthritis (RA) remains poorly understood.
Methods: Utilizing a two-phase study design, we performed high-throughput RNA sequencing on peripheral blood mononuclear cells (PBMCs) from three treatment-naïve RA patients and three healthy controls (HCs), followed by validation in an independent cohort of 32 RA patients and 32 HCs using real-time quantitative polymerase chain reaction (RT-qPCR).
Results: A total of 157 circRNAs were differentially expressed between RA patients and HCs, including 91 upregulated and 66 downregulated circRNAs. Six circRNAs, including hsa_circ_0001394, hsa_circ_0001998, hsa_circ_0009172, hsa_circ_0006732, circRNA2842, and circRNA8330, were further confirmed to be upregulated in RA. Among them, hsa_circ_0001394 demonstrated perfect sensitivity (100%), and hsa_circ_0001998 exhibited perfect specificity (100%) in distinguishing RA from HCs. All six circRNAs showed considerable diagnostic performance, with area under the curve (AUC) values ranging from 0.794 to 0.993. Additionally, specific circRNAs correlated significantly with established serological markers: hsa_circ_0009172 expression was negatively associated with anti-cyclic citrullinated peptide (anti-CCP) antibody titers, whereas hsa_circ_0001998 expression correlated positively with rheumatoid factor (RF). Pathway enrichment analysis suggested that these differentially expressed circRNAs may participate in RA pathogenesis through key pathways like Wnt, calcium and VEGF signaling.
Conclusion: Our study identifies several novel circRNAs with high diagnostic utility for RA, highlighting their potential as promising biomarkers and therapeutic targets.
Keywords: rheumatoid arthritis, circular RNAs, PBMCs, biomarker