Abstract
BackgroundMicroRNAs (miRNAs) have been reported as deregulated in active brain lesions derived from patients with multiple sclerosis (MS). In there, these post-transcriptional regulators may elicit very important effects but proper identification of miRNA candidates as potential biomarkers and/or therapeutic targets is scarcely available.ObjectiveThe aim of the study was to detect the presence of a set of candidate miRNAs in cell-free cerebrospinal fluid (CSF) and to determine their association with gadolinium-enhancing (Gd+) lesions in order to assess their value as biomarkers of MS activity.MethodsAssessment of 28 miRNA candidates in cell-free CSF collected from 46 patients with MS (26 Gd+ and 20 Gd− patients) was performed by TaqMan assays and qPCR. Variations in their relative abundance were analyzed by the Mann-Whitney U test and further evaluated by receiver operating characteristic (ROC) analysis. Signaling pathways and biological functions of miRNAs were analyzed using bioinformatic tools (miRTarBase, Enrichr, REVIGO, and Cytoscape softwares).ResultsSeven out of 28 miRNA candidates were detected in at least 75% of CSF samples. Consistent increase of miR-21 and miR-146a/b was found in Gd+ MS patients. This increase was in parallel to the number of Gd+ lesions and neurofilament light chain (NF-L) levels. Gene Ontology enrichment analysis revealed that the target genes of these miRNAs are involved in biological processes of key relevance such as apoptosis, cell migration and proliferation, and in cytokine-mediated signaling pathways.ConclusionLevels of miR-21 and miR-146a/b in cell-free CSF may represent valuable biomarkers to identify patients with active MS lesions.
Highlights
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) characterized by inflammation, demyelination, and neurodegeneration
This study aims to test the presence of a set of deregulated miRNAs, previously found in active multiple sclerosis (MS) lesions from brain biopsies [8], in cell-free cerebrospinal fluid (CSF) of MS patients, and to study their association with the presence of gadolinium-enhancing (Gd+) lesions to assess their value as biomarkers of new MS lesion formation
Seven of 28 miRNAs reported as deregulated in active MS lesions (9) were detected in at least 75% of CSF samples, assessed in triplicate by Ct values lower than 37
Summary
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) characterized by inflammation, demyelination, and neurodegeneration. Several studies in MS have analyzed the role or profile of miRNAs in different tissues including peripheral blood mononuclear cells (PBMCs) [6], CD4+ cells [7], and MS brain lesions [8]. They can be released extracellularly into body fluids such as plasma or cerebrospinal fluid (CSF), where they remain stable [9,10,11,12]. MicroRNAs (miRNAs) have been reported as deregulated in active brain lesions derived from patients with multiple sclerosis (MS) In there, these post-transcriptional regulators may elicit very important effects but proper identification of miRNA candidates as potential biomarkers and/or therapeutic targets is scarcely available
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