Journal
JOURNAL OF AUTOIMMUNITY
Volume 101, Issue -, Pages 17-25Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2019.04.002
Keywords
Multiple sclerosis (MS); MicroRNAs (miRNAs); Small non-coding RNAs (sncRNAs); Biomarkers; RNA-Based therapeutics
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Funding
- Karolinska Institutet
- Swedish Research Council
- Swedish Society for Medical Research
- Margaretha of Ugglas Foundation
- Swedish Association for Persons with Neurological Disabilities
- Swedish Brain Foundation
- Swedish MS Foundation
- Stockholm County Council (ALF project)
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Multiple sclerosis (MS) is a leading cause of progressive disability among young adults caused by inflammation, demyelination and axonal loss in the central nervous system. Small non-coding RNAs (sncRNAs) are important regulators of various biological processes and could therefore play important roles in MS. Over the past decade, a large number of studies investigated sncRNAs in MS patients, focusing primarily on microRNAs (miRNAs). Overwhelming 500 miRNAs have been reported as dysregulated in MS. Nevertheless, owing to a large heterogeneity between studies it is challenging to evaluate the reproducibility of findings, in turn hampering our knowledge about the functional roles of miRNAs in disease. We systematically searched main databases and evaluated results from all studies that examined sncRNAs in MS to date (n = 61) and provided a detailed overview of experimental design and findings of these studies. We focused on the mechanisms of the most dysregulated sncRNAs and used predicted targets of the most dysregulated sncRNAs as input for functional enrichment analysis to highlight affected pathways. The prime affected pathway was TGF-beta signaling. This multifunctional cytokine is important in the differentiation and function of T helper type 17 (Th17) and regulatory T (Treg) cells, with opposing functions in the disease. Recent studies demonstrate the importance of miRNAs in controlling the balance between Th17/Th1 cells and Tregs and, importantly, the potential to exploit this paradigm for therapeutic purposes. Additionally, some of the discussed miRNAs could potentially serve as biomarkers of disease. In order to assist researchers in evaluating the evidence of a particular sncRNA in the pathogenesis of MS, we provide a detailed overview of experimental design and findings of these studies to date.
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