Jiwei Zhao, Tianjun Zhu, Qiu Liao, Jijia Sun, Fuqun Liu
{"title":"循环exo-miRNA-27a-5p是托法替尼治疗类风湿性关节炎反应的一种新的生物标志物。","authors":"Jiwei Zhao, Tianjun Zhu, Qiu Liao, Jijia Sun, Fuqun Liu","doi":"10.1186/s41927-025-00502-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>This study suggests that circulating exo-miR-27a-5p is a novel non-invasive biomarker to monitor the response to tofacitinib treatment.</p>","PeriodicalId":9150,"journal":{"name":"BMC Rheumatology","volume":"9 1","pages":"49"},"PeriodicalIF":2.1000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036121/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis.\",\"authors\":\"Jiwei Zhao, Tianjun Zhu, Qiu Liao, Jijia Sun, Fuqun Liu\",\"doi\":\"10.1186/s41927-025-00502-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>This study suggests that circulating exo-miR-27a-5p is a novel non-invasive biomarker to monitor the response to tofacitinib treatment.</p>\",\"PeriodicalId\":9150,\"journal\":{\"name\":\"BMC Rheumatology\",\"volume\":\"9 1\",\"pages\":\"49\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-04-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036121/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Rheumatology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s41927-025-00502-1\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Rheumatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s41927-025-00502-1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Circulating exo-miRNA-27a-5p is a novel biomarker of the tofacitinib treatment response in rheumatoid arthritis.
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.