Human miR-26a-5p regulates the glutamate transporter SLC1A1 (EAAT3) expression. Relevance in multiple sclerosis

Biochim Biophys Acta Mol Basis Dis. 2018 Jan;1864(1):317-323. doi: 10.1016/j.bbadis.2017.09.024. Epub 2017 Sep 28.

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by chronic inflammation, demyelination and scarring as well as a broad spectrum of signs and symptoms. MicroRNA plays pivotal roles in cellular and developmental processes by regulating gene expression at the post-transcriptional level. Increasing evidence suggests the involvement of microRNAs in the pathogenesis of neurodegenerative diseases, including MS. We have already found that the expression of a specific miRNA, hsa-mir-26a-5p (miR-26a), changed during INF-β treatment in responder Relapsing-Remitting MS patients. Functional annotations of mir-26a targets revealed that a number of genes were implicated in Glutamate Receptor Signaling pathway, which is notoriously altered in neurodegenerative diseases as MS. In this study, the different potential targets were subjected to a validation test based on luciferase reporter constructs transfected in an oligodendroglial cell line. In this functional screening, miR-26a was able to interact with SLC1A1 3' UTR suppressing the reporter activity. Transfection of a miR-26a mimic was then shown to decrease the endogenous SLC1A1 mRNA. Afterward, we have evaluated in blood platelets from interferon-β treated Multiple Sclerosis patients the expression of miR-26a and SLC1A1, finding not only their converse expression, but also a responsiveness to interferon-β therapy. Overall, these data suggest that mir-26a and SLC1A1 may play a role in the MS pathogenesis, and may be potential targets for the development of new biomarkers and/or therapeutic tools.

Keywords: INF-β treatment; Multiple sclerosis; SLC1A1; microRNA.

MeSH terms

  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Cells, Cultured
  • Excitatory Amino Acid Transporter 3 / genetics*
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon-beta / therapeutic use
  • MicroRNAs / physiology*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / pathology
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Excitatory Amino Acid Transporter 3
  • MIRN26A microRNA, human
  • MicroRNAs
  • SLC1A1 protein, human
  • Interferon-beta