YY1-induced upregulation of lncRNA NEAT1 contributes to OGD/R injury-induced inflammatory response in cerebral microglial cells via Wnt/β-catenin signaling pathway

In Vitro Cell Dev Biol Anim. 2019 Aug;55(7):501-511. doi: 10.1007/s11626-019-00375-y. Epub 2019 Jul 8.

Abstract

Stroke can lead to the serious long-term neurological disability. The dysregulation of long non-coding RNAs (lncRNAs) has been proven to be a pivotal factor for the progression of ischemic stroke. However, it is largely unknown whether lncRNAs regulated the OGD/R injury of cerebral microglial cells. In this study, we designed experiments to reveal the role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in the OGD/R injury of microglial cells. We found that NEAT1 contributed to the OGD/R injury and neuroinflammation damage in microglial cells. Moreover, the molecular mechanism involved in the NEAT1-mediated OGD/R injury. Mechanism investigation revealed that NEAT1 was upregulated by the transcription factor YY1. Moreover, Western blot analysis suggested that NEAT1 enhance the protein levels of core factors of Wnt/β-catenin signaling pathway, indicating that NEAT1 contributed to the activation of Wnt/β-catenin signaling pathway. Rescue assays were carried out in the microglial cells treated with OGD/R. The results showed that NEAT1 regulated the OGD/R injury and neuroinflammation damage via Wnt/β-catenin signaling pathway. In conclusion, our findings suggested that YY1-induced upregulation of NEAT1 contributed to the OGD/R injury and neuroinflammation damage of microglial cells via Wnt/β-catenin signaling pathway.

Keywords: Microglial cells; OGD/R injury; Wnt/β-catenin signaling pathway; YY1; lncRNA NEAT1.

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation / genetics*
  • Microglia / cytology
  • Microglia / pathology*
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • Rats
  • Stroke / genetics
  • Up-Regulation / genetics
  • Wnt Signaling Pathway / genetics*
  • Wnt Signaling Pathway / physiology
  • YY1 Transcription Factor / genetics*

Substances

  • RNA, Long Noncoding
  • YY1 Transcription Factor
  • Yy1 protein, rat