miR-106b inhibits tau phosphorylation at Tyr18 by targeting Fyn in a model of Alzheimer's disease

Biochem Biophys Res Commun. 2016 Sep 16;478(2):852-7. doi: 10.1016/j.bbrc.2016.08.037. Epub 2016 Aug 9.


Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by β-amyloid deposits and neurofibrillary tangles consisting of hyperphosphorylated tau protein. Increasing evidence has revealed that microRNAs (miRNAs) are implicated in the pathogenesis of AD. However, the effect of miRNAs on abnormal tau phosphorylation remains largely unclear so far. In this study, we investigated the role of miR-106b in tau phosphorylation and identified a new molecular mechanism of the hyperphosphorylation of tau. The results of qRT-PCR showed that the expression level of miR-106b was decreased, but Fyn was increased in the temporal cortex of AD patients. Overexpression of miR-106b inhibited Aβ1-42-induced tau phosphorylation at Tyr18 in SH-SY5Y cells stably expressing tau (SH-SY5Y/tau), whereas no changes were observed in tau phosphorylation at Ser396/404. Dual-luciferase reporter gene assay validated that Fyn was a direct target gene of miR-106b. In addition, western blot analysis revealed that Fyn protein expression was suppressed when SH-SY5Y cells were transfected with miR-106b mimics. Endogenous Fyn expression was knockdown by transfection with a small interfering RNA specific for Fyn (si-Fyn). The phosphorylation level of tau at Tyr 18 was decreased in the si-Fyn group compared with the negative control group, but the inhibitory effect of si-Fyn on tau phosphorylation was attenuated when miR-106b expression was inhibited. Taken together, these data suggest that miR-106b inhibits Aβ1-42-induced tau phosphorylation at Tyr18 by targeting Fyn. Our findings extend the knowledge about the regulation of tau phosphorylation and the regulatory mechanism of Fyn gene expression.

Keywords: Alzheimer's disease; Fyn; Phosphorylation; Tau; miR-106b.

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / pharmacology
  • Base Sequence
  • Case-Control Studies
  • Cell Line, Tumor
  • Frontal Lobe / metabolism
  • Frontal Lobe / pathology
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Biological
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Oligoribonucleotides, Antisense / genetics
  • Oligoribonucleotides, Antisense / metabolism
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational*
  • Proto-Oncogene Proteins c-fyn / antagonists & inhibitors
  • Proto-Oncogene Proteins c-fyn / genetics*
  • Proto-Oncogene Proteins c-fyn / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Temporal Lobe / metabolism
  • Temporal Lobe / pathology
  • Tyrosine / metabolism*
  • tau Proteins / genetics
  • tau Proteins / metabolism*


  • Amyloid beta-Peptides
  • MIRN106 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides, Antisense
  • Peptide Fragments
  • RNA, Small Interfering
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Tyrosine
  • Luciferases
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn