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Cell Cycle ; 20(1): 54-64, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33345691

RESUMO

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.


Assuntos
Isquemia Encefálica/genética , Caderinas/genética , Regulação para Baixo/genética , MicroRNAs/genética , Traumatismo por Reperfusão/genética , Animais , Apoptose/genética , Sobrevivência Celular/genética , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/genética , Masculino , NF-kappa B/genética , Neurônios/patologia , Estresse Oxidativo/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima/genética
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