miR-194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

J Cell Biochem. 2020 Jun;121(5-6):3278-3285. doi: 10.1002/jcb.29598. Epub 2020 Jan 13.

Abstract

The emerging role of microRNAs (miRNAs) have been deeply explored in multiple diseases including neuropathic pain. miR-194 was widely reported to be a tumor suppressor and was related to the inflammatory response. The critical role of neuroinflammation on neuropathic pain leads to a thinking about the relationship between miR-194 and neuropathic pain. However, the function of miR-194 in neuropathic pain remains unknown. This study was aimed to explore the relationship between miR-194 and neuropathic pain progression by chronic sciatic nerve injury (CCI). miR-194 abnormally downregulated in the CCI model rat and its overexpression significantly alleviates neuroinflammation in vivo. We predict Forkhead box protein A1 (FOXA1) as a direct target of miR-194, whose restoration can markedly reverse the effects of miR-194 on neuropathic pain. Overall, our study demonstrated a novel mechanism of neuropathic pain progression that miR-194 alleviates neuropathic pain via targeting FOXA1 and preventing neuroinflammation by downregulating inflammatory cytokines containing cyclooxygenase 2, interleukin 6 (IL-6), and IL-10 in vivo, which can be reversed by the overexpression of FOXA1.

Keywords: FOXA1; miR-194; neuroinflammation; neuropathic pain.

MeSH terms

  • Animals
  • Behavior, Animal
  • Disease Progression
  • Down-Regulation
  • Female
  • HEK293 Cells
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Injections, Spinal
  • MicroRNAs / metabolism*
  • Neuralgia / metabolism*
  • Peripheral Nerve Injuries / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / injuries

Substances

  • FOXA1 protein, human
  • Foxa1 protein, rat
  • Hepatocyte Nuclear Factor 3-alpha
  • MIRN194 microRNA, human
  • MIRN194 microRNA, rat
  • MicroRNAs