MicroRNA-27a Regulates Ferroptosis Through SLC7A11 to Aggravate Cerebral ischemia-reperfusion Injury.

Abstract

Cerebral ischemia-reperfusion (I/R) injury is an inevitable issue in the treatment of ischemic stroke, which has a high disability rate and seriously threatens the living quality of patients. Previous studies have demonstrated that ferroptosis, which plays a crucial role in ischemia-reperfusion injury, can be accelerated by microRNA-27a (miR-27a). However, the mechanism by which miR-27a regulates ferroptosis in cerebral ischemia-reperfusion injury remains unknown. In this study, Male Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO), then restored blood flow. Neurological function score and TTC staining were used to evaluate brain tissue injury and the infarct volume. The relative expression level of miR-27a was detected by qPCR. The relative expression levels of glutathione peroxidase 4(GPx4), solute carrier family 7 member 11 (SLC7A11) proteins were analyzed by Western Blot. The contents of GSH, Fe and malonaldehyde (MDA) were detected by corresponding detection kits, and the target gene of miR-27a was confirmed by dual luciferase reporter gene technique. It was found the relative expression level of miR-27a was increased and ferroptosis was aggravated as reperfusion time went by. Also, brain tissue injury and ferroptosis were exacerbated with agomiR-27a intervention, while these effects were reversed with antagomiR-27a intervention. In addition, the combined intervention of agomiR-27a and Fer-1 alleviated the brain tissue injury and ferroptosis. The results of dual luciferase reporter gene technique indicated SLC7A11 as the target gene of miR-27a. In the current study, miR-27a upregulates ferroptosis to aggravate cerebral ischemia-reperfusion injury by SLC7A11.

• Authors: Lijun Zhu, Ziren Feng, Jing Zhang, Lin Du, Aiguo Meng
• Journal: Neurochemical research (Neurochem Res) Vol. 48 Issue 5 Pg. 1370-1381 (May 2023) ISSN: 1573-6903 [Electronic] United States
• PMID: 36456793 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Luciferases
• MicroRNAs
• MIRN27 microRNA, rat
• Slc7a11 protein, rat

Topics

• Animals
• Male
• Rats
• Brain Ischemia (metabolism)
• Ferroptosis
• Infarction, Middle Cerebral Artery (metabolism)
• Luciferases (pharmacology)
• MicroRNAs (genetics, metabolism)
• Rats, Sprague-Dawley
• Reperfusion Injury (genetics, metabolism)