PMID- 36434857 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230111 IS - 1532-8511 (Electronic) IS - 1052-3057 (Linking) VI - 32 IP - 1 DP - 2023 Jan TI - MiR-342-5p protects neurons from cerebral ischemia induced-apoptosis through regulation of Akt/NF-kappaB pathways by targeting CCAR2. PG - 106901 LID - S1052-3057(22)00593-6 [pii] LID - 10.1016/j.jstrokecerebrovasdis.2022.106901 [doi] AB - 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-kappaB 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. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Zhu, Haochun AU - Zhu H AD - Department of Neurology, General Hospital of Hebi Coal Industry Group Co., Ltd., No. 84, Hongqi Street, Hebi, Henan 458000, China. Electronic address: zhc53927185@163.com. FAU - Zhang, Yanhua AU - Zhang Y AD - Department of Neurology, General Hospital of Hebi Coal Industry Group Co., Ltd., No. 84, Hongqi Street, Hebi, Henan 458000, China. Electronic address: hnhbzyh@163.com. FAU - Zhu, Yanling AU - Zhu Y AD - Department of Neurology, General Hospital of Hebi Coal Industry Group Co., Ltd., No. 84, Hongqi Street, Hebi, Henan 458000, China. Electronic address: zhuyanling9877@163.com. LA - eng PT - Journal Article DEP - 20221123 PL - United States TA - J Stroke Cerebrovasc Dis JT - Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association JID - 9111633 RN - 0 (NF-kappa B) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 0 (MicroRNAs) RN - S88TT14065 (Oxygen) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Mice MH - Animals MH - NF-kappa B/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - *MicroRNAs/genetics/metabolism MH - *Brain Ischemia/genetics/metabolism MH - Infarction, Middle Cerebral Artery/genetics/metabolism MH - Oxygen/metabolism MH - Apoptosis MH - Neurons/metabolism MH - Glucose MH - *Reperfusion Injury/metabolism OTO - NOTNLM OT - Akt/NF-kB OT - CCAR2 OT - MCAO OT - MiR-342-5p OT - Stroke COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2022/11/27 06:00 MHDA- 2023/01/11 06:00 CRDT- 2022/11/26 18:15 PHST- 2022/08/11 00:00 [received] PHST- 2022/10/24 00:00 [revised] PHST- 2022/11/16 00:00 [accepted] PHST- 2022/11/27 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/11/26 18:15 [entrez] AID - S1052-3057(22)00593-6 [pii] AID - 10.1016/j.jstrokecerebrovasdis.2022.106901 [doi] PST - ppublish SO - J Stroke Cerebrovasc Dis. 2023 Jan;32(1):106901. doi: 10.1016/j.jstrokecerebrovasdis.2022.106901. Epub 2022 Nov 23.