MiR-342-5p protects neurons from cerebral ischemia induced-apoptosis through regulation of Akt/NF-KB pathways by targeting CCAR2

Objectives: Ischemic stroke causes high morbidity, mortality and health burden in the world. MiR-342-5p was associated with Alzheimer's disease and cardio-protection. Herein, we aimed to reveal effects of miR-342-5p on cerebral ischemia injury as well as novel targets for stroke. Materials and methods: AgomiR-342-5p was intracerebroventricularly injected into the middle cerebral artery occlusion (MCAO) mouse models to evaluate functions of miR-342-5p on cerebral ischemia. RT-qPCR and western blot assays were used to evaluate genes expression. Oxygen-glucose deprivation (OGD) was used as an in vitro model for ischemia. Viability and apoptosis ratio of neurons was evaluated by CCK-8, LDH release detection, and flow cytometry. The potential targets of miR-342-5p were predicted by Targetscan, and their interaction was confirmed by luciferase assay. Results: The intervention of miR-342-5p effectively attenuated ischemic injury in MCAO mice. MiR-342-5p overexpression could protect neurons against OGD-induced injury, as revealed by increased cell viability and BCL2 expression, and decreased LDH release, apoptosis ratio, and BAX expression in OGD-induced neurons. Mechanically, miR-342-5p could directly bound with CCAR2 to inhibit its expression. Overexpressing CARR2 aggravated the OGD-induced injury of neurons, which was partly restrained by overexpressing miR-342-5p reversed. Furthermore, miR-342-5p/CARR2 axis regulates Akt/NF-KB signaling pathway in vitro as well as in vivo cerebral ischemia models. Conclusions: MiR-342-5p inhibited neuron apoptosis by regulating Akt/ NF-kB signaling pathway via CCAR2 suppression. Our findings revealed the neuroprotection of miR-342-5p in cerebral ischemia. Keywords: Stroke-MCAO-MiR-342-5p-CCAR2-Akt/NF-kB (c) 2022 Elsevier Inc. All rights reserved.