Elsevier

Journal of Autoimmunity

Volume 101, July 2019, Pages 17-25
Journal of Autoimmunity

Small non-coding RNAs as important players, biomarkers and therapeutic targets in multiple sclerosis: A comprehensive overview

https://doi.org/10.1016/j.jaut.2019.04.002Get rights and content
Under a Creative Commons license
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Highlights

  • Our review represents the most detailed and complete review of sncRNA studies in MS.

  • Other classes of dysregulated sncRNAs in MS: snoRNAs, scaRNAs, sdRNAs, viral miRNAs.

  • The prime miRNA-affected pathway in MS was TGF-β signaling.

  • Circulating miRNAs show great potential as MS biomarkers.

  • MiRNAs potential can be exploited for therapeutic purposes.

Abstract

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-β 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.

Keywords

Multiple sclerosis (MS)
MicroRNAs (miRNAs)
Small non-coding RNAs (sncRNAs)
Biomarkers
RNA-Based therapeutics

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