MicroRNA-130a regulates neurological deficit and angiogenesis in rats with ischaemic stroke by targeting XIAP

J Cell Mol Med. 2020 Sep;24(18):10987-11000. doi: 10.1111/jcmm.15732. Epub 2020 Aug 13.

Abstract

MicroRNAs (miRNAs) have already been proposed to be implicated in the development of ischaemic stroke. We aim to investigate the role of miR-130a in the neurological deficit and angiogenesis in rats with ischaemic stroke by regulating X-linked inhibitor of apoptosis protein (XIAP). Middle cerebral artery occlusion (MCAO) models were established by suture-occluded method, and MCAO rats were then treated with miR-130a mimics/inhibitors or/and altered XIAP for detection of changes of rats' neurological function, nerve damage and angiogenesis in MCAO rats. The oxygen-glucose deprivation (OGD) cellular models were established and respectively treated to determine the roles of miR-130a and XIAP in neuronal viability and apoptosis. The expression levels of miR-130a and XIAP in brain tissues of MCAO rats and OGD-treated neurons were detected. The binding site between miR-130a and XIAP was verified by luciferase activity assay. MiR-130a was overexpressed while XIAP was down-regulated in MCAO rats and OGD-treated neurons. In animal models, suppressed miR-130a improved neurological function, alleviated nerve damage and increased new vessels in brain tissues of rats with MCAO. In cellular models, miR-130a inhibition promoted neuronal viability and suppressed apoptosis. Inhibited XIAP reversed the effect of inhibited miR-130a in both MCAO rats and OGD-treated neurons. XIAP was identified as a target of miR-130a. Our study reveals that miR-130a regulates neurological deficit and angiogenesis in rats with MCAO by targeting XIAP.

Keywords: X-linked inhibitor of apoptosis protein; angiogenesis; ischaemic stroke; microRNA-130a; middle cerebral artery occlusion; neurological deficit.

MeSH terms

  • Animals
  • Apoptosis
  • Binding Sites
  • Body Water
  • Brain Chemistry
  • Brain Damage, Chronic / etiology
  • Brain Damage, Chronic / genetics*
  • Brain Damage, Chronic / physiopathology
  • Cell Hypoxia
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacology
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / genetics*
  • Infarction, Middle Cerebral Artery / physiopathology
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Inhibitor of Apoptosis Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Morris Water Maze Test
  • Neovascularization, Physiologic / drug effects
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Oxygen / pharmacology
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Rats

Substances

  • Inhibitor of Apoptosis Proteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Xiap protein, rat
  • Glucose
  • Oxygen