Knockdown Ezh2 Attenuates Cerebral Ischemia-Reperfusion Injury Via Regulating Microrna-30d-3p Methylation And Usp22

Objective: Cerebral ischemia-reperfusion (I/R) injury remains a major challenge in clinic. The enhancer of zest homolog-2 (EZH2) has been demonstrated to participate in the development of brain injury. Nevertheless, its molecular mechanism has not been fully elucidated. Therein, we aim to investigate the effect of EZH2 on oxidative stress and nerve injury of cerebral I/R injury by modulating microRNA (miR)-30d-3p methylation and ubiquitin-specific protease 22 (USP22).Methods: Cerebral I/R model of CD1 mice was established by modified Longa method to realize transient middle cerebral artery occlusion. We conducted EZH2 inhibition or miR-30d-3p overexpression assays to determine walking coordination, learning and memory ability, neurological injury score, serum inflammatory response, brain tissue oxidative stress injury, cerebral infarction area, and brain tissue cell apoptosis in cerebral I/R injury mice. MiR-30d-3p methylation level was tested. EZH2, miR-30d-3p and USP22 levels were tested in brain tissues. Finally, the relationship between miR-30d-3p and USP22 was verified.Results: MiR-30d-3p decreased while EZH2 and USP22 increased in cerebral I/R injury mice. Up-regulating miR30d-3p and down-regulating EZH2 promoted walking coordination, learning and memory ability, decreased neurological injury score and serum inflammatory response, ameliorated oxidative stress injury, reduced cerebral infarction area and cell apoptosis in cerebral I/R injury mice. Downregulation of miR-30d-3p reversed the effect of downregulated EZH2 on oxidative stress and nerve injury in mice with cerebral I/R injury. EZH2 promoted miR-30d-3p methylation to target USP22.Conclusion: Silencing EZH2 suppresses miR-30d-3p methylation and then ameliorates oxidative stress and nerve injury via regulating USP22 in cerebral I/R injury mice, which may be a potential candidate for treatment of cerebral I/R injury.