title: Circulating microRNAs as biomarkers in progressive multiple sclerosis.
abstract: BACKGROUND
  In multiple sclerosis (MS), microRNA (miRNA) dysregulation is mostly reported in different immune cells, but less information is available on circulating miRNAs that exert strong biomarker potential due to their exceptional stability in body fluids.
  
  
  OBJECTIVE
  The aim of this study was to profile expression of circulating miRNAs in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) and assess their association with neurological worsening.
  
  
  METHODS
  The expressions of 84 different miRNAs were profiled in serum of 83 subjects (62 MS and 21 controls) using miScript miRNA techniques. First, they were screened on 18 PPMS and 10 controls; thereafter, 10 most aberrantly expressed miRNAs were validated on a larger cohort.
  
  
  RESULTS
  In comparison with controls, upregulation of miR-191-5p was found in both progressive MS subtypes, while miR-376c-3p was overexpressed only in PPMS. Additionally, upregulation of miR-128-3p and miR-24-3p was detected in PPMS when compared to controls and SPMS. Progression index correlated with miR-128-3p in PPMS and miR-375 in SPMS.
  
  
  CONCLUSIONS
  We detected overexpression of four miRNAs that have not been previously associated with progressive forms of MS. The increased expression of circulating miR-191-5p seems to be associated with progressive forms of MS, while miR-128-3p seems to be associated mostly with PPMS.
authors.affiliation: Neuroimmunology Unit, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Julia
authors.initials: J
authors.lastname: Vistbakka
authors.affiliation: Neuroimmunology Unit, School of Medicine, University of Tampere, Tampere, Finland/Department of Neurology, Tampere University Hospital, Tampere, Finland.
authors.forename: Irina
authors.initials: I
authors.lastname: Elovaara
authors.affiliation: Department of Clinical Chemistry, School of Medicine, University of Tampere, Tampere, Finland/Fimlab Laboratories, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: Neuroimmunology Unit, School of Medicine, University of Tampere, Tampere, Finland/Department of Neurology, Tampere University Hospital, Tampere, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Hagman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D000074166:Circulating MicroRNA / Q000097:blood*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015415:Biomarkers; D000074166:Circulating MicroRNA; D035683:MicroRNAs
keywords: Multiple sclerosis; PPMS; SPMS; biomarkers; circulating microRNA; miR-128-3p; miR-191-5p; miR-24-3p; miR-376c-3p