Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing

Mult Scler. 2014 Mar;20(3):295-303. doi: 10.1177/1352458513496343. Epub 2013 Jul 8.

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.

Keywords: Multiple sclerosis; biomarker; clinically isolated syndrome; microRNAs; microarray; next-generation sequencing; real-time polymerase chain reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Demyelinating Diseases / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Multiple Sclerosis, Relapsing-Remitting / genetics*
  • Oligonucleotide Array Sequence Analysis

Substances

  • MicroRNAs