lncRNA MALAT1 contributes to neuropathic pain development through regulating miR-129-5p/HMGB1 axis in a rat model of chronic constriction injury

Int J Neurosci. 2020 Dec;130(12):1215-1224. doi: 10.1080/00207454.2020.1731508. Epub 2020 Feb 25.

Abstract

Backgrounds: Mounting studies pay attention to the functional roles of long non-coding RNAs (lncRNAs) in many human diseases including neuropathic pain. LncRNA MALAT1 has been indicated to serve as a critical mediator in neuropathic pain with unclear mechanisms. The present study aims to explore the functional roles of MALAT1 in neuropathic pain progression and the related mechanisms.Methods: Bilateral sciatic nerves were ligated to induce chronic constriction injury (CCI) in order to establish the neuropathic pain rat model followed by behavioral tests, RT-qPCR, Western blotting, and ELISA. Dual luciferase activity assay was performed to determine the binding effect between MALAT1 or HMGB1 and miR-129-5p.Results: The mRNA levels of MALAT1 were significantly enhanced in CCI rats. MALAT1 inhibition repressed the development of neuropathic pain and neuroinflammation. Additionally, miR-129-5p was decreased and HMGB1 was increased, both of which could be rectified by MALAT1 inhibition. Meanwhile, MALAT1 targeted miR-129-5p/HMGB1 axis. Finally, miR-129-5p suppression attenuated the inhibitory effect of MALAT1 inhibition on neuropathic pain and neuroinflammation development in CCI rats.Conclusion: The present study demonstrates that MALAT1 might modulate neuropathic pain via targeting miR-129-5p/HMGB1 axis. These findings may lead to a promising and efficacious clinical approach for the treatment of neuropathic pain.

Keywords: HMGB1; MALAT1; Neuropathic pain; chronic constriction injury; miR-129-5p.

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Constriction
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Regulation
  • HMGB1 Protein / metabolism*
  • Inflammation / metabolism*
  • Inflammation / prevention & control
  • MicroRNAs / metabolism*
  • Neuralgia / etiology
  • Neuralgia / metabolism*
  • Neuralgia / prevention & control
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Sciatic Nerve / injuries

Substances

  • HMGB1 Protein
  • Hbp1 protein, rat
  • MALAT1 long noncoding RNA, rat
  • MIRN129 microRNA, rat
  • MicroRNAs
  • RNA, Long Noncoding