MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40
10.3349/ymj.2022.63.4.389
- Author:
Lingjiang SUN
1
;
Dandan JI
;
Feng ZHI
;
Yu FANG
;
Zigang ZHU
;
Tong NI
;
Qin ZHU
;
Jie BAO
Author Information
1. Department of Critical Care Medicine, Wuxi Second People’s Hospital, Wuxi, Jiangsu, China
- Publication Type:Original Article
- From:Yonsei Medical Journal
2022;63(4):389-398
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:Cerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species (ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40) in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion (I/R) injury.
Materials and Methods:A mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemia in vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation (OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. The relationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays.
Results:Bhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40 overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p was verified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/ R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reverse the effects of miR-494-3p overexpression on ROS production and cell apoptosis.
Conclusion:MiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.
