Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis
One of the most promising exosomal biomarker materials involves small noncoding RNA.2 It is well established that numerous non–protein‐coding RNA molecules are involved in fundamental biological processes via regulation of gene expression and protein synthesis. In this regard, particularly well understood is the function of microRNAs (miRNAs). miRNAs are endogenous ∼22nt noncoding RNAs that post‐transcriptionally regulate gene expression and function.6 They provide a guide for proteins involved in the function of RNA‐induced silencing complexes that degrade complimentary target mRNAs or block their translation. In MS and its animal model, experimental autoimmune encephalomyelitis, several miRNAs have already been found to correlate with immune cell polarization and their effector functions.7 Thus, miRNAs provide a new direction in our understanding of immune regulation in MS. The role of extracellular miRNAs remains a fascinating new aspect of their biology, which is still poorly understood. Until recently, most studies focused on the analysis of free‐floating extracellular miRNAs in biological fluids. Measurement of miRNAs within exosomes likely provides a more reliable approach than the analysis of free‐floating miRNAs, because exosomes effectively separate and protect their content from the extracellular environment, allowing intact cargo to be safely transported.12 In addition, the exosome miRNA profile is prespecified and is not random.2 This refers to the finding that exosomes target selected cells and induce changes that are preprogrammed in the exosome host cells. Thus, analysis of exosomal miRNAs might provide important data on the regulation of immune reactions in MS.
In this study, using a next generation sequencing (NGS) method, we were able to characterize the total transcriptome profile of circulating exosomes. We have demonstrated large quantities of miRNAs within serum exosomes. In particular, we identified 4 exosomal miRNAs that were significantly downregulated in MS patients during both clinical and radiological flare of the disease.