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Plasma miR-26a as a Diagnostic Biomarker Regulates Cytokine Expression in Systemic Juvenile Idiopathic Arthritis
Juan Sun1, Miao Feng1, Fengqi Wu1
1From the Department of Molecular Immunology, and the Department of Immunology and Rheumatology, Capital Institute of Pediatrics, Beijing, China.J. Sun*, MD, Department of Molecular Immunology, Capital Institute of Pediatrics; M. Feng*, PhD, Department of Molecular Immunology, Capital Institute of Pediatrics; F. Wu, MD, Department of Immunology and Rheumatology, Capital Institute of Pediatrics; X. Ma, MD, Department of Molecular Immunology, Capital Institute of Pediatrics; J. Lu, MD, Department of Molecular Immunology, Capital Institute of Pediatrics; M. Kang, PhD, Department of Immunology and Rheumatology, Capital Institute of Pediatrics; Z. Liu, MD, Department of Molecular Immunology, Capital Institute of Pediatrics.
Objective:
We sought to identify specific microRNA (miRNA) for systemic juvenile idiopathic arthritis (sJIA) and to determine the involvement of these miRNA in regulating the expression of cytokines.
Methods:
Microarray profiling was performed to identify differentially expressed miRNA in sJIA plasma. Levels of candidate miRNA and mRNA were assessed by real-time PCR, and cytokines were measured by ELISA. Dual-luciferase reporter assay was used to validate the direct interaction between miR-26a and interleukin 6 (IL-6).
Results:
Forty-eight miRNA were differentially expressed in the plasma of patients with sJIA compared with healthy controls (HC). Five miRNA were selected for further validation. The expression level of miR-26a was exclusively elevated in the plasma of patients with sJIA as compared with 4 rheumatic diseases and 2 subtypes of JIA (oligoarticular and polyarticular). The levels of IL-6, IL-1β, and tumor necrosis factor-α in the plasma of patients with sJIA were increased, and only IL-6 presented a positive correlation with miR-26a (r = 0.539, p < 0.0001). After stimulation with IL-6, miR-26a expression was upregulated in THP-1 cells, while the supernatant level of IL-6 was downregulated by transfection of miR-26a mimics. Consistently, direct target relationship between miR-26a and IL-6 was confirmed.
Conclusion:
This study demonstrates that miR-26a is expressed specifically and highly in sJIA plasma and suggests that miR-26a may regulate the levels of cytokines in sJIA. Our findings highlight miR-26a as a potential biomarker for the diagnosis as well as differential diagnosis of sJIA.
Insights
MicroRNA-26a is highly expressed in systemic juvenile idiopathic arthritis (sJIA) plasma and may regulate cytokine levels. This suggests miR-26a could be a diagnostic biomarker for sJIA.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Systemic juvenile idiopathic arthritis (sJIA) is a severe form of childhood arthritis.
- Identifying specific biomarkers for sJIA is crucial for diagnosis and treatment.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) in sJIA plasma.
- To investigate the role of these miRNAs in regulating cytokine expression in sJIA.
Main Methods:
- Microarray profiling to identify differentially expressed miRNAs in sJIA plasma.
- Real-time PCR and ELISA to quantify miRNA, mRNA, and cytokine levels.
- Dual-luciferase reporter assay to confirm miRNA-target interactions.
Main Results:
- Forty-eight miRNAs were differentially expressed in sJIA patients compared to healthy controls.
- miR-26a was significantly elevated in sJIA plasma and correlated positively with IL-6 levels.
- miR-26a directly targets and regulates IL-6 expression.
Conclusions:
- miR-26a is specifically and highly expressed in sJIA plasma.
- miR-26a may play a role in regulating cytokine levels in sJIA.
- miR-26a shows potential as a diagnostic and differential diagnostic biomarker for sJIA.
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