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

• Published in: Cell cycle (Georgetown, Tex.) Vol. 20; no. 1; pp. 54 - 64
• Main Authors: Yang, Chun-Chun, Wei, Xiang-Pin, Fu, Xian-Ming, Qian, Ling-Tao, Xie, Lan-Jun, Liu, Hong-Bo, Li, Gang, Li, Xin-Gang, Zeng, Xian-Wei
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 2021
• Subjects: 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; Neurons - pathology; NF-kappa B - genetics; Oxidative Stress - genetics; Rats; Rats, Sprague-Dawley; Reperfusion Injury - genetics; Research Paper; Up-Regulation - genetics; pathological damage; microRNA-20a; Cerebral ischemia/reperfusion injury; cadherin-1; oxidative stress; nerve injury
• ISSN: 1551-4005; 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2020.1856498

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.