miR-23a-3p and miR-181a-5p modulate SNAP-25 expression

PLoS One. 2023 Jan 17;18(1):e0279961. doi: 10.1371/journal.pone.0279961. eCollection 2023.

Abstract

SNAP-25 protein is a key protein of the SNARE complex that is involved in synaptic vesicles fusion with plasma membranes and neurotransmitter release, playing a fundamental role in neural plasticity. Recently the concentration of three specific miRNAs-miR-27b-3p, miR-181a-5p and miR-23a-3p -was found to be associated with a specific SNAP-25 polymorphism (rs363050). in silico analysis showed that all the three miRNAs target SNAP-25, but the effect of the interaction between these miRNAs and the 3'UTR of SNAP-25 mRNA is currently unknown. For this reason, we verified in vitro whether miR-27b-3p, miR-181a-5p and miR-23a-3p modulate SNAP-25 gene and protein expression. Initial experiments using miRNAs-co-transfected Vero cells and SNAP-25 3'UTR luciferase reporter plasmids showed that miR-181a-5p (p≤0.01) and miR-23a-3p (p<0.05), but not miR-27b-3p, modulate the luciferase signal, indicating that these two miRNAs bind the SNAP-25 3'UTR. Results obtained using human oligodendroglial cell line (MO3.13) transfected with miR-181a-5p or miR-27b-3p confirmed that miR-181a-5p and miR-23a-3p regulate SNAP-25 gene and protein expression. Interestingly, the two miRNAs modulate in an opposite way SNAP-25, as miR-181a-5p significantly increases (p<0.0005), whereas miR-23a-3p decreases (p<0.0005) its expression. These results for the first time describe the ability of miR-181a-5p and miR-23a-3p to modulate SNAP-25 expression, suggesting their possible use as biomarkers or as therapeutical targets for diseases in which SNAP-25 expression is altered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Chlorocebus aethiops
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Synaptosomal-Associated Protein 25* / genetics
  • Vero Cells

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Synaptosomal-Associated Protein 25
  • SNAP25 protein, human
  • MIrn181 microRNA, human

Grants and funding

This study was financial funded by Ministero della Salute (Award number: Ricerca Corrente 2020-2022) and by Fondazione Cariplo (Award number: 2017-0622). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.