miR-29c regulates NAV3 protein expression in a transgenic mouse model of Alzheimer's disease

Brain Res. 2015 Oct 22:1624:95-102. doi: 10.1016/j.brainres.2015.07.022. Epub 2015 Jul 23.

Abstract

The microRNA-29 family (miRNA-29s) has three mature members, miR-29a, miR-29b and miR-29c, which have been implicated in the regulation of the pathogenesis of Alzheimer's disease (AD). The miR-29 family members exhibit differential regulation in various diseases and different subcellular distribution. In the present study, we initially investigated differential expression of miR-29c in the hippocampus and the frontal cortex of the young APPswe/PSΔE9 mouse brain, accompanied by inverse expression of neurone navigator 3 (NAV3), a regulator of axon guidance. We observed that miR-29c directly mediated downregulation of NAV3 protein expression in vitro. The mouse NAV3 mRNA has a functional miR-29c binding site in the 3' UTR, which localized in the position between 830-836 bp of 3'UTR region, slightly different from human NAV3 mRNA binding site. These observations suggest that miR-29c may be involved in neurodegenerative processes by regulating NAV3 expression in the young AD mouse.

Keywords: APPswe/PSΔE9 mice; Alzheimer׳s disease; NAV3 protein; miR-29c; microRNAs.

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / physiology
  • Age Factors
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression Regulation / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutation / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroblastoma / pathology
  • Presenilin-1 / genetics
  • Protein Binding / genetics
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism

Substances

  • 3' Untranslated Regions
  • Amyloid beta-Protein Precursor
  • MIRN29 microRNA, mouse
  • Membrane Proteins
  • MicroRNAs
  • NAV3 protein, human
  • Nerve Tissue Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • RNA, Small Nuclear
  • Green Fluorescent Proteins