Circ_0005075 targeting miR-151a-3p promotes neuropathic pain in CCI rats via inducing NOTCH2 expression

Gene. 2021 Jan 30:767:145079. doi: 10.1016/j.gene.2020.145079. Epub 2020 Aug 27.

Abstract

Neuropathic pain is a most challenging diseases worldwide, caused by the injury of nerve system. CircularRNAs (circRNAs) are revealed to be involved in various diseases, includingneuropathic pain. However, the waycircRNAsparticipate in the progress ofneuropathic painstill needs further study. Identifyingthe possible circRNAexpression patterns of neuropathic painis of great significance to understand its underlying mechanism. Previously, circ_0005075 has been regarded as an important oncogene in multiple cancers and it has been characterized as an inflammation‑associated circRNA in various processes. Nevertheless, the functional role of circ_0005075 in neuropathic pain development is still poorly known. In our present study, we observed circ_0005075 was obviously increased in CCI rat models. Knockdown of circ_0005075 repressed thebehaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, loss of circ_0005075 could repress the neuroinflammation via targeting COX-2, IL-6 and TNF-α whereas inducing IL-10 in vivo. Additionally, we predicted miR-151a-3p as the potential target of circ_0005075 using bioinformatics analysis. We displayed that miR-151a-3p was greatly reduced in CCI rats and circ_0005075 reversed the repressive effect of miR-151a-3p on neuropathic pain. For another, NOTCH2 has been shown to induce a variety of intracellular responses correlated withneuropathic pain. Here, we found NOTCH2 expression was strongly induced in CCI rats and miR-151a-3p. In addition, circ_0005075 significantly rescued NOTCH2 expression, which could be repressed by miR-151a-3p. To sum up, we indicated that loss ofcirc_0005075relieved neuropathic pain progression by inducement of miR-151a-3p and inactivation of NOTCH2 signaling.

Keywords: Circ_0005075; NOTCH2; Neuropathic pain; miR-151a-3p.

MeSH terms

  • Animals
  • Disease Progression
  • Inflammation / metabolism
  • Interleukin-6 / genetics
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neuralgia / genetics*
  • Neuralgia / metabolism
  • RNA, Circular / genetics*
  • RNA, Long Noncoding / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-6
  • MIRN151 microRNA, rat
  • MicroRNAs
  • Notch2 protein, rat
  • RNA, Circular
  • RNA, Long Noncoding
  • Receptor, Notch2
  • Tumor Necrosis Factor-alpha