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Published on: July 23, 2012
Circulating microRNAs as biomarkers in progressive multiple sclerosis
Julia Vistbakka1, Irina Elovaara2, Terho Lehtimäki3
1Neuroimmunology Unit, School of Medicine, University of Tampere, Tampere, Finland.
Background:
In multiple sclerosis (MS), microRNA (miRNA) dysregulation is mostly reported in different immune cells, but less information is available on circulating miRNAs that exert strong biomarker potential due to their exceptional stability in body fluids.
Objective:
The aim of this study was to profile expression of circulating miRNAs in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) and assess their association with neurological worsening.
Methods:
The expressions of 84 different miRNAs were profiled in serum of 83 subjects (62 MS and 21 controls) using miScript miRNA techniques. First, they were screened on 18 PPMS and 10 controls; thereafter, 10 most aberrantly expressed miRNAs were validated on a larger cohort.
Results:
In comparison with controls, upregulation of miR-191-5p was found in both progressive MS subtypes, while miR-376c-3p was overexpressed only in PPMS. Additionally, upregulation of miR-128-3p and miR-24-3p was detected in PPMS when compared to controls and SPMS. Progression index correlated with miR-128-3p in PPMS and miR-375 in SPMS.
Conclusion:
We detected overexpression of four miRNAs that have not been previously associated with progressive forms of MS. The increased expression of circulating miR-191-5p seems to be associated with progressive forms of MS, while miR-128-3p seems to be associated mostly with PPMS.
Insights
This study identified four circulating microRNAs (miRNAs) linked to progressive multiple sclerosis (MS). Increased levels of miR-191-5p indicate progressive MS, while miR-128-3p is notably associated with primary progressive MS (PPMS).
Area of Science:
- Neuroimmunology
- Molecular Biology
- Biomarker Discovery
Background:
- MicroRNA (miRNA) dysregulation is implicated in multiple sclerosis (MS) pathogenesis, primarily studied in immune cells.
- Circulating miRNAs offer biomarker potential due to their stability in biological fluids, yet their role in progressive MS remains underexplored.
Purpose of the Study:
- To profile circulating miRNA expression in primary progressive MS (PPMS) and secondary progressive MS (SPMS).
- To investigate the association between altered miRNA levels and neurological worsening in progressive MS subtypes.
Main Methods:
- Serum samples from 62 MS patients (PPMS and SPMS) and 21 controls were analyzed for 84 miRNA expressions using miScript miRNA technology.
- Initial screening on a small cohort was followed by validation of the most dysregulated miRNAs in a larger group.
Main Results:
- Upregulation of miR-191-5p was observed in both PPMS and SPMS compared to controls.
- miR-128-3p and miR-24-3p were significantly upregulated in PPMS versus controls and SPMS.
- miR-376c-3p was exclusively overexpressed in PPMS.
- Progression index correlated with miR-128-3p in PPMS and miR-375 in SPMS.
Conclusions:
- Four novel miRNAs associated with progressive MS were identified.
- Elevated circulating miR-191-5p is linked to progressive MS.
- miR-128-3p shows a strong association with PPMS, suggesting potential as a subtype-specific biomarker.
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