Differentially expressed microRNA in multiple sclerosis: A window into pathogenesis?

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Abstract

MicroRNA are small non-coding RNA that mediate mRNA translation repression or mRNA degradation, and thereby refine protein expression levels. More than 30–60% of all genes are regulated by microRNA. Exploring disease-related microRNA signatures is an emerging tool in biomarker discovery, and silencing has already been used in a clinical phase 2a trial. As microRNA regulate translation of more than 100 genes, they could also provide a focused insight into important pathways, and offer a better understanding of diseases with heterogeneous pathogenesis. The number of studies investigating microRNA related to multiple sclerosis has increased significantly in recent years. Differentially expressed microRNA have been identified in the whole blood, serum, plasma, cerebrospinal fluid, peripheral blood mononuclear cells, blood-derived cell subsets and brain lesions of patients with multiple sclerosis. Most studies applied a non-candidate approach of screening by microarray and validation by quantitative polymerase chain reaction or next generation sequencing; others used a candidate-driven approach. Despite a relatively high number of multiple sclerosis-associated microRNA, just a few could be repeatedly found, even if similar biological materials were examined. Only part of the identified microRNA has been extensively studied, and the biological function has not been explored in the majority. Some of the microRNA related to multiple sclerosis are also differentially expressed in other autoimmune diseases or autoimmune models. In the present review, we discuss microRNA related to disease compartments, activity and phenotype. We also focus on several microRNA with well-defined functions, or because of particular interest due to either validation by several independent studies or in-depth exploration of function.

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