Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. (March 2014)

• Record Type: Journal Article
• Authors: Keller, Andreas; Leidinger, Petra; Steinmeyer, Florian; Stähler, Cord; Franke, Andre; Hemmrich-Stanisak, Georg; Kappel, Andreas; Wright, Ian; Dörr, Jan; Paul, Friedemann; Diem, Ricarda; Tocariu-Krick, Beatrice; Meder, Benjamin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens
• Is Part Of: Multiple sclerosis. Volume 20:Number 3(2014)
• Page Start: 295
• Page End: 303
• Publication Date: 2014-03
• Subjects: Multiple sclerosis -- clinically isolated syndrome -- microRNAs -- biomarker -- next-generation sequencing -- microarray -- real-time polymerase chain reaction; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458513496343
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: MicroRNAs (miRNAs) are short, noncoding RNAs with gene regulatory functions whose expression profiles may serve as disease biomarkers. Objective: The objective of this study was to perform a comprehensive analysis of miRNA expression profiles in blood of patients with a clinically isolated syndrome (CIS) or relapsing–remitting multiple sclerosis (RRMS) including next-generation sequencing (NGS). Methods: miRNA expression was analyzed in whole blood samples from treatment-naïve patients with CIS ( n = 25) or RRMS ( n = 25) and 50 healthy controls by NGS, microarray analysis, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: In patients with CIS/RRMS, NGS and microarray analysis identified 38 and eight significantly deregulated miRNAs, respectively. Three of these miRNAs were found to be significantly up- (hsa-miR-16-2-3p) or downregulated (hsa-miR-20a-5p, hsa-miR-7-1-3p) by both methods. Another five of the miRNAs significantly deregulated in the NGS screen showed the same direction of regulation in the microarray analysis. qRT-PCR confirmed the direction of regulation for all eight and was significant for three miRNAs. Conclusions: This study identifies a set of miRNAs deregulated in CIS/RRMS and reconfirms the previously reported underexpression of hsa-miR-20a-5p in MS. hsa-miR-20a-5p and the other validated miRNAs may represent promising candidates for future evaluation as biomarkers for MS and could be of relevance in the pathophysiology of this disease.