Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis
Abstract Background Effective biological markers able to monitor the response of Janus kinase inhibitor (JAKi) are lacking. Exosomal microRNAs (exomiRNAs) can alter their expression during treatment and are ideal biomarkers for therapeutic interventions. In this study, we explored potential biomarke...
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BMC
2025-04-01
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| Series: | BMC Rheumatology |
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| Online Access: | https://doi.org/10.1186/s41927-025-00502-1 |
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| author | Jiwei Zhao Tianjun Zhu Qiu Liao Jijia Sun Fuqun Liu |
| author_facet | Jiwei Zhao Tianjun Zhu Qiu Liao Jijia Sun Fuqun Liu |
| author_sort | Jiwei Zhao |
| collection | DOAJ |
| description | Abstract Background Effective biological markers able to monitor the response of Janus kinase inhibitor (JAKi) are lacking. Exosomal microRNAs (exomiRNAs) can alter their expression during treatment and are ideal biomarkers for therapeutic interventions. In this study, we explored potential biomarkers for monitoring tofacitinib treatment response in patients with RA. Methods Peripheral blood mononuclear cells (PBMCs) were collected from 35 healthy controls (HCs) and 74 patients with methotrexate (MTX)-resistant new-onset RA. We analyzed the profiles of exomiRNAs using next-generation sequencing (NGS) and verified them using quantitative real-time polymerase chain reaction (qRT-PCR). The functional roles of the selected exomiRNAs were analyzed using bioinformatics tools. Potential exomiRNAs were validated in MTX-resistant RA patients treated with tofacitinib for 3 months. Results Fifty-six differentially expressed exomiRNAs were identified. High expressions of the exo-(miR-548ah-3p, miR-378 g, miR-27a-5p, and miR-30c-2-3p) were validated by qRT-PCR. Enrichment analysis indicated that these exomiRNAs may regulate immune cells and mediate immune responses. Exo-miR-27a-5p levels significantly decreased after tofacitinib treatment (p < 0.0001) and showed a strong correlation with the DAS28, RF and ESR. Receiver operating characteristic curve analysis showed that changes in the expression levels of exo-miR-27a-5p were significantly correlated with tofacitinib therapy (AUC = 0.92, p < 0.0001). Conclusions This study suggests that circulating exo-miR-27a-5p is a novel non-invasive biomarker to monitor the response to tofacitinib treatment. |
| format | Article |
| id | doaj-art-b78b4e18ba7b4da9a60482d1104c67f9 |
| institution | OA Journals |
| issn | 2520-1026 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Rheumatology |
| spelling | doaj-art-b78b4e18ba7b4da9a60482d1104c67f92025-08-20T02:10:52ZengBMCBMC Rheumatology2520-10262025-04-019111310.1186/s41927-025-00502-1Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritisJiwei Zhao0Tianjun Zhu1Qiu Liao2Jijia Sun3Fuqun Liu4Department of Rheumatology and Immunology, Lishui District Traditional Hospital of Chinese MedicineDepartment of Rheumatology and Immunology, Lishui District Traditional Hospital of Chinese MedicineDepartment of Orthopaedics, Lishui District Traditional Hospital of Chinese MedicineTeaching and Research Section of the Chinese Materia School of Pharmacy, Shanghai University of Traditional Chinese MedicineDepartment of Rheumatology and Immunology, Lishui District Traditional Hospital of Chinese MedicineAbstract Background Effective biological markers able to monitor the response of Janus kinase inhibitor (JAKi) are lacking. Exosomal microRNAs (exomiRNAs) can alter their expression during treatment and are ideal biomarkers for therapeutic interventions. In this study, we explored potential biomarkers for monitoring tofacitinib treatment response in patients with RA. Methods Peripheral blood mononuclear cells (PBMCs) were collected from 35 healthy controls (HCs) and 74 patients with methotrexate (MTX)-resistant new-onset RA. We analyzed the profiles of exomiRNAs using next-generation sequencing (NGS) and verified them using quantitative real-time polymerase chain reaction (qRT-PCR). The functional roles of the selected exomiRNAs were analyzed using bioinformatics tools. Potential exomiRNAs were validated in MTX-resistant RA patients treated with tofacitinib for 3 months. Results Fifty-six differentially expressed exomiRNAs were identified. High expressions of the exo-(miR-548ah-3p, miR-378 g, miR-27a-5p, and miR-30c-2-3p) were validated by qRT-PCR. Enrichment analysis indicated that these exomiRNAs may regulate immune cells and mediate immune responses. Exo-miR-27a-5p levels significantly decreased after tofacitinib treatment (p < 0.0001) and showed a strong correlation with the DAS28, RF and ESR. Receiver operating characteristic curve analysis showed that changes in the expression levels of exo-miR-27a-5p were significantly correlated with tofacitinib therapy (AUC = 0.92, p < 0.0001). Conclusions This study suggests that circulating exo-miR-27a-5p is a novel non-invasive biomarker to monitor the response to tofacitinib treatment.https://doi.org/10.1186/s41927-025-00502-1Rheumatoid arthritisCirculating exosomesMiRNAsBiomarkerTofacitinib |
| spellingShingle | Jiwei Zhao Tianjun Zhu Qiu Liao Jijia Sun Fuqun Liu Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis BMC Rheumatology Rheumatoid arthritis Circulating exosomes MiRNAs Biomarker Tofacitinib |
| title | Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis |
| title_full | Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis |
| title_fullStr | Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis |
| title_full_unstemmed | Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis |
| title_short | Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis |
| title_sort | circulating exo mirna 27a 5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis |
| topic | Rheumatoid arthritis Circulating exosomes MiRNAs Biomarker Tofacitinib |
| url | https://doi.org/10.1186/s41927-025-00502-1 |
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