Inhibition of miR-200b/miR-429 contributes to neuropathic pain development through targeting zinc finger E box binding protein-1

J Cell Physiol. 2018 Jun;233(6):4815-4824. doi: 10.1002/jcp.26284. Epub 2018 Jan 15.

Abstract

Many studies have reported that microRNAs participate in neuropathic pain development. Previously, miR-200b and miR-429 are reported to be involved in various diseases. In our current study, we focused on their roles in neuropathic pain and we found that miR-200b and miR-429 were significantly decreased in chronic constriction injury (CCI) rat spinal cords and isolated microglials. miR-200b and miR-429 overexpression were able to relieve neuropathic pain through modulating PWT and PWL in CCI rats. Meanwhile, we observed that both miR-200b and miR-429 upregulation could repress neuroinflammation via inhibiting inflammatory cytokines such as IL-6, IL-1β, and TNF-α in CCI rats. By carry out bioinformatics technology, Zinc finger E box binding protein-1 (ZEB1) was predicted as target of miR-200b, and miR-429 and dual-luciferase reporter assays confirmed the correlation between them. ZEB1 has been reported to regulate a lot of diseases. Here, we found that ZEB1 was greatly increased in CCI rats and miR-200b and miR-429 overexpression markedly suppressed ZEB1 mRNA expression in rat microglial cells. In addition, knockdown of ZEB1 can reduce neuropathic pain development and co-transfection of LV-anti-miR-200b/miR-429 reversed this phenomenon in vivo. Taken these together, our results suggested that miR-200b/miR-429 can serve as an important regulator of neuropathic pain development by targeting ZEB1.

Keywords: ZEB1; miR-200b; miR-429; neuropathic pain.

MeSH terms

  • Animals
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Behavior, Animal
  • Cytokines / metabolism
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microglia / metabolism*
  • Pain Perception
  • Pain Threshold*
  • Rats, Sprague-Dawley
  • Sciatica / genetics
  • Sciatica / metabolism*
  • Sciatica / physiopathology
  • Sciatica / prevention & control
  • Signal Transduction
  • Spinal Cord / metabolism*
  • Spinal Cord / physiopathology
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • Antagomirs
  • Cytokines
  • Inflammation Mediators
  • MIRN200 microRNA, rat
  • MicroRNAs
  • Zinc Finger E-box-Binding Homeobox 1