Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Potenza, Nicoletta1
  • Mosca, Nicola1
  • Mondola, Paolo2
  • Damiano, Simona2
  • Russo, Aniello1
  • De Felice, Bruna3
  • 1 DISTABIF, University of Campania "Luigi Vanvitelli", Italy. , (Italy)
  • 2 Department of Clinical Medicine and Surgery, University of Naples "Federico II", Italy. , (Italy)
  • 3 DISTABIF, University of Campania "Luigi Vanvitelli", Italy. Electronic address: [email protected] , (Italy)
Type
Published Article
Journal
Biochimica et Biophysica Acta
Publisher
Elsevier
Publication Date
Jan 01, 2018
Volume
1864
Issue
1
Pages
317–323
Identifiers
DOI: 10.1016/j.bbadis.2017.09.024
PMID: 28962897
Source
Medline
Keywords
License
Unknown

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.

Report this publication

Statistics

Seen <100 times