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

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.

• Authors: Xiaodan Tan, Wenjia Guo, Zhe Peng, Chao Gu, Pu Xiang, Yujun Tu, Huizhi Fei, Xia Liu, Yi Lu, Miaomiao Li, Hong Wang, Ying Luo, Junqing Yang
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 192 Pg. 114694 (10 2021) ISSN: 1873-2968 [Electronic] England
• PMID: 34324865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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