LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s

Aging (Albany NY). 2020 Jan 26;12(2):1778-1791. doi: 10.18632/aging.102712. Epub 2020 Jan 26.

Abstract

Brain microvascular endothelial cell (BMEC) survival and angiogenesis after ischemic stroke has great significance for improving the prognosis of stroke. Abnormal variants of lncRNAs are closely associated with stroke. In this study, we examined the effects and molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis, migration, and angiogenesis of oxygen-glucose deprivation (OGD)-treated BMECs. We found that DANCR expression significantly increased at 2, 4, 6, 8, and 10 h after OGD. DANCR overexpression promoted cell viability, migration, and angiogenesis in OGD-treated BMECs. Additionally, we found that X-box binding protein l splicing (XBP1s) expression was positively correlated with DANCR expression. DANCR overexpression promoted XBP1s expression in OGD-treated BMECs. Silenced XBP1s reversed the effect of DANCR in OGD-treated BMECs. Furthermore, we found that microRNA (miR)-33a-5p bound to DANCR and the 3'-UTR of XBP1. miR-33a-5p overexpression inhibited proliferation, migration, angiogenesis, and XBP1s expression in OGD-treated DANCR-overexpressing BMECs, reversing the protective effect of DANCR. Finally, we found that XBP1s expression promoted proliferation, migration, and angiogenesis, reversing the damaging effect of miR-33a-5p. In conclusion, DANCR enhanced survival and angiogenesis in OGD-treated BMECs through the miR-33a-5p/XBP1s axis.

Keywords: DANCR; X-box binding protein l splicing; brain microvascular endothelial cell; ischemic stroke; miR-33a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Brain / blood supply
  • Brain / metabolism
  • Brain / pathology
  • Cell Movement
  • Cell Proliferation / genetics
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Humans
  • MicroRNAs / genetics*
  • Microvessels / metabolism*
  • Oxygen / metabolism*
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • X-Box Binding Protein 1 / genetics*

Substances

  • 3' Untranslated Regions
  • DANCR long noncoding RNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Glucose
  • Oxygen