title: Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing.
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.
authors.affiliation: Department of Human Genetics, Saarland University, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.forename: Florian
authors.initials: F
authors.lastname: Steinmeyer
authors.forename: Cord
authors.initials: C
authors.lastname: Stähler
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Georg
authors.initials: G
authors.lastname: Hemmrich-Stanisak
authors.forename: Andreas
authors.initials: A
authors.lastname: Kappel
authors.forename: Ian
authors.initials: I
authors.lastname: Wright
authors.forename: Jan
authors.initials: J
authors.lastname: Dörr
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.forename: Ricarda
authors.initials: R
authors.lastname: Diem
authors.forename: Beatrice
authors.initials: B
authors.lastname: Tocariu-Krick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meder
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
mesh_terms: D019295:Computational Biology; D003711:Demyelinating Diseases / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D035683:MicroRNAs
keywords: Multiple sclerosis; biomarker; clinically isolated syndrome; microRNAs; microarray; next-generation sequencing; real-time polymerase chain reaction