MicroRNA-365 Knockdown Prevents Ischemic Neuronal Injury by Activating Oxidation Resistance 1-Mediated Antioxidant Signals

• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2019,（5）
• 页码范围: 815-825
• 页数: 11页
• 语种: 英文

摘要

MicroRNA-365 (miR-365) is upregulated in the ischemic brain and is involved in oxidative damage in the diabetic rat.However,it is unclear whether miR-365 regulates oxidative stress (OS)-mediated neuronal damage after ischemia.Here,we used a transient middle cerebral artery occlusion model in rats and the hydrogen peroxide-induced OS model in primary cultured neurons to assess the roles of miR-365 in neuronal damage.We found that miR-365 exacerbated ischemic brain injury and OS-induced neuronal damage and was associated with a reduced expression of OXR1 (Oxidation Resistance 1).In contrast,miR-365 antagomir alleviated both the brain injury and OXR1 reduction.Luciferase assays indicated that miR-365 inhibited OXR1 expression by directly targeting the 3'-untranslated region of Oxrl.Furthermore,knockdown of OXR1 abolished the neuroprotective and antioxidant effects of the miR-365 antagomir.Our results suggest that miR-365 upregulation increases oxidative injury by inhibiting OXR1 expression,while its downregulation protects neurons from oxidative death by enhancing OXR1-mediated antioxidant signals.