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

作者：Keller Andreas; Leidinger Petra; Steinmeyer Florian; Staehler Cord; Franke Andre; Hemmrich Stanisak Georg; Kappel Andreas; Wright Ian; Doerr Jan; Paul Friedemann; Diem Ricarda; Tocariu Krick Beatrice; Meder Benjamin; Backes Christina; Meese Eckart; Ruprecht Klemens^*

来源：Multiple Sclerosis, 2014, 20(3): 295-303.

DOI：10.1177/1352458513496343

• real-time polymerase chain reaction
• microarray
• biomarker
• Multiple sclerosis
• next-generation sequencing
• clinically isolated syndrome
• microRNAs

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-naive 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.

• 出版日期2014-3