Down-regulating microRNA-20a regulates CDH1 to protect against cerebral ischemia/reperfusion injury in rats

Cell Cycle. 2021 Jan;20(1):54-64. doi: 10.1080/15384101.2020.1856498. Epub 2020 Dec 19.

Abstract

Studies have extensively focused on the involvement of microRNAs (miRNAs) in cerebral ischemia/reperfusion (I/R) injury but not much on the specific role of miR-20a. Hence, this study is purposed to decipher whether miR-20a could regulate cadherin 1 (CDH1) to affect cerebral I/R injury in rats. Rat transient middle cerebral artery occlusion model (MCAO) was established. Rats were injected with lentiviral solution containing miR-20a inhibitor, or overexpressed CDH1 or combined depleted miR-20a and CDH1 to explore their roles in cerebral I/R injury. Oxidative stress-related factors, miR-20a, CDH1, nuclear factor-kappaB (NF-κB) and Nestin expression in brain tissues were detected by RT-qPCR and western blot assay. The target relation between miR-20a and CDH1 was predicted by online website and further confirmed by luciferase activity assay. In rats with cerebral I/R injury, increased miR-20a and decreased CDH1 were found in brain tissues. Reduction of miR-20a or elevation of CDH1 attenuated behavior function in MCAO rats. Inhibiting miR-20a or restoring CDH1 restrained oxidative stress, attenuated pathological damage of neurons, promoted neuron survival, and down-regulated NF-κB and Nestin expression in brain tissues of MCAO rats. CDH1 was determined to a target gene of miR-20a. This study elucidates that down-regulating miR-20a elevates CDH1 to protect neurons from cerebral I/R injury, which paves a new way for treatment of cerebral I/R injury.

Keywords: Cerebral ischemia/reperfusion injury; cadherin-1; microRNA-20a; nerve injury; oxidative stress; pathological damage.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Brain Ischemia / genetics*
  • Cadherins / genetics*
  • Cell Survival / genetics
  • Disease Models, Animal
  • Down-Regulation / genetics*
  • Infarction, Middle Cerebral Artery / genetics
  • Male
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • Neurons / pathology
  • Oxidative Stress / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / genetics*
  • Up-Regulation / genetics

Substances

  • CDH1 protein, rat
  • Cadherins
  • MIRN20 microRNA, rat
  • MicroRNAs
  • NF-kappa B