MiR-342-5p protects neurons from cerebral ischemia induced-apoptosis through regulation of Akt/NF-κB 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-κB 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.

MiR-410 exerts neuroprotective effects in a cellular model of Parkinson's disease induced by 6-hydroxydopamine via inhibiting the PTEN/AKT/mTOR signaling pathway.

Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by loss of dopaminergic neurons in the substantia nigra. Recently, microRNAs (miRNAs) were emerging as important mediators in dopaminergic neuron biology. This study determined miR-410 expression in the 6-hydroxydopamine (6-OHDA)-induced in vitro cellular model of PD and explored the mechanistic role of miR-410 in the modulation of neuronal cell viability and apoptosis. Our data showed that 6-OHDA concentration-dependently suppressed neuronal cell viability and miR-410 expression in SH-SY5Y and PC12 cells. Overexpression of miR-410 partially restored the effects of 6-OHDA on neuronal cell viability, apoptosis, capsase-3 activity as well as reactive oxygen species (ROS) production. On the other hand, inhibition of miR-410 decreased neuronal cell viability and increased apoptotic rates, capase-3 activity as well as ROS production. Furthermore, the potential targets of miR-410 were predicted by TargetScan tool, and we verified that phosphatase and tensin homolog (PTEN) was a target of miR-410 as confirmed by the dual-luciferase reporter assay. MiR-410 overexpression attenuated PTEN expression and mediated the effects in the 6-OHDA-treated cells via targeting PTEN in SH-SY5Y and PC12 cells. Furthermore, 6-OHDA treatment suppressed the protein expression of phosphorylated AKT and phosphorylated mTOR, which was partially attenuated by miR-410 overexpression in SH-SY5Y and PC12 cells. MiR-410 overexpression increased phosphorylated AKT and phosphorylated mTOR protein expression, and this effect was attenuated by PTEN overexpression in both SH-SY5Y and PC12 cells. Collectively, this is the first study to demonstrate the neuroprotective effects of miR-410 in a 6-OHDA-induced cellular model of PD, and our data implied that miR-410 exerted its neuroprotective effects via regulating PTEN/AKT/mTOR signaling axis. The present study may suggest new paradigm to study the pathology of PD.