Downregulated circular RNA zRANB1 mediates Wnt5a/β-Catenin signaling to promote neuropathic pain via miR-24-3p/LPAR3 axis in CCI rat models

Gene. 2020 Nov 30:761:145038. doi: 10.1016/j.gene.2020.145038. Epub 2020 Aug 8.

Abstract

Neuropathic pain, which results from impairment of the somatosensory system, has affected about 8% population around the world and leads to considerable burdens for patients and world health care system. However, its underlying mechanisms remain poorly understood. In this study, we hypothesized that miR-24-3p was involved in the progression of neuropathic pain in CCI rat models. By measuring miR-24-3p expression in CCI rats, we found that miR-24-3p expression was increased in CCI rats, suggesting miR-24-3p might participate in neuropathic pain progression. Next, by conducting a serial in vitro and vivo experiments, we found that miR-24-3p regulated Wnt5a/β-Catenin Signaling levels to promote neuropathic pain progression via targeting LPAR3 in CCI rats. Furthermore, we explored the upstream regulator of miR-24-3p by conducting bioinformatics analysis, we found that circular RNA cZRANB1 might sponge to miR-24-3p. Then we applied biotinylated RNA pull-down and luciferase reporter assays to assess the association between cZRANB1 and miR-24-3p. It was found that cZRANB1 mediated LPAR3 expression via sponging miR-24-3p. Collectively, our study suggests that cZRNAB1 regulated Wnt5a/β-Catenin Signaling expression via miR-24-3p/LPAR3 axis in CCI rat models.

Keywords: Circular RNA; LPAR3; Neuropathic pain; cZRANB1; miR-24-3p.

MeSH terms

  • Animals
  • Constriction, Pathologic / genetics
  • Disease Progression
  • Endopeptidases
  • Gene Expression Regulation / genetics
  • HEK293 Cells
  • Humans
  • Inflammation / genetics
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neuralgia / genetics*
  • RNA, Circular / genetics
  • RNA, Long Noncoding / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Lysophosphatidic Acid / genetics*
  • Receptors, Lysophosphatidic Acid / metabolism
  • Signal Transduction / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Ubiquitin Thiolesterase / genetics
  • Wnt Signaling Pathway / genetics
  • Wnt-5a Protein / genetics
  • Wnt-5a Protein / metabolism
  • beta Catenin / metabolism

Substances

  • MIRN24 microRNA, rat
  • MicroRNAs
  • RNA, Circular
  • RNA, Long Noncoding
  • Receptors, Lysophosphatidic Acid
  • Tumor Necrosis Factor-alpha
  • WNT5A protein, human
  • Wnt-5a Protein
  • beta Catenin
  • Endopeptidases
  • ZRANB1 protein, human
  • Ubiquitin Thiolesterase