MiR-101 relates to chronic peripheral neuropathic pain through targeting KPNB1 and regulating NF-κB signaling

Kaohsiung J Med Sci. 2019 Mar;35(3):139-145. doi: 10.1002/kjm2.12025.

Abstract

Accumulating evidences indicates that chronic neuropathic pain is a kind of neuro-immune disorder with enhanced activation of the immune system. Although the prevalence is very high, neuropathic pain remains extremely difficult to cure. miRNAs are a group of short nonprotein coding RNAs, regulating target genes expression via targeting 3'-untranslated region. More and more research indicates that altered miRNAs expression profile relates to the pathogenesis of neuropathic pain. In this study, we firstly detected the expression of six candidate miRNAs in the plasma samples from 23 patients with neuropathic pain and 10 healthy controls. Subsequently, the level of miR-132 and miR-101 was detected in the sural nerve biopsies. We found miR-101 level was significantly repressed in both the plasma samples and sural nerve biopsies from neuropathic pain patients. Predicted by bioinformatics tools and confirmed by dual luciferase assay and immunoblotting, we identified that KPNB1 is a direct target of miR-101. The negative correlation between miR-101 and KPNB1 was also confirmed in the sural nerve biopsies, and miR-101 reduction relates to the activation of NF-κB signaling in vivo and in vitro which contributes to the pathogenesis of neuropathic pain.

Keywords: KPNB1; NF-κB; miRNA; neuropathic pain.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Base Sequence
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Chronic Pain / blood
  • Chronic Pain / genetics*
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Interleukin-1beta / metabolism
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • NF-kappa B / metabolism*
  • Neuralgia / blood
  • Neuralgia / genetics*
  • Signal Transduction*
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • beta Karyopherins / genetics
  • beta Karyopherins / metabolism*

Substances

  • 3' Untranslated Regions
  • Interleukin-1beta
  • KPNB1 protein, human
  • MIRN101 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RELA protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • beta Karyopherins