LncRNA-Malat1 down-regulates miR-211-5p expression to promote neuronal damage from cerebral ischemia reperfusion injury

Biochem Pharmacol. 2021 Oct:192:114694. doi: 10.1016/j.bcp.2021.114694. Epub 2021 Jul 26.

Abstract

Based on the previous studies, this study was carried out to explore the interaction of LncRNA-Malat1/miR-211-5p in cerebral ischemia reperfusion injury (CIRI). Firstly, the expression changes of LncRNA-MALAT1 and miR-211-5p in ischemia patients' blood were determined, and the binding sites of them were predicted by bioinformatics. Furthermore, middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established in adult male SD rats, and primary neuronal oxygen-glucose deprivation/reoxygen-glucose reoxygenation (OGD/R) was established in vitro. The results showed that LncRNA-MALAT1 was significantly up-regulated and miR-211-5p down-regulated in the peripheral blood of patients with ischemic stroke, and the expression changes were negatively correlated. Bioinformatics prediction results showed that LncRNA-MALAT1 had a binding site with miR-211-5p. We also found that LncRNA-Malat1 was significantly up-regulated while miR-211-5p down-regulated in rat cortex tissue and primary neurons treated with OGD/R. In addition, lentivirus interfered with LV-Malat1-RNAi decreased the expression of LncRNA-Malat1 and promoted the up-regulation of miR-211-5p. Combination of LV-Malat1-RNAi and miR-211-5p inhibitor significantly reversed the protective effect of down-regulation of LncRNA-Malat1. Inhibition of LncRNA-Malat1 expression alleviated the neurological deficit score after MCAO/R, improved histopathological damage, and reduced the size of cerebral infarction. Combined administration of LV-Malat1-RNAi + Antagomir-211-5p reversed these effects above. In short, our data suggest that LncRNA-Malat is involved in the occurrence and development of cerebral ischemia reperfusion injury by acting on miR-211-5p and is then regulating the expression of COX-2.

Keywords: Apoptosis; CIRI; COX-2; Inflammation; LncRNA-Malat1; miR-211-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Cells, Cultured
  • Down-Regulation / physiology
  • Female
  • Gene Expression
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • Neurons / metabolism*
  • Neurons / pathology
  • RNA, Long Noncoding / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology

Substances

  • MALAT1 long non-coding RNA, human
  • MIRN211 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding