Yinbao Qi1,2,3, Ruobing Qian2,3, Li Jia2,3, Xiaorui Fei2,3, Dong Zhang2,3, Yiming Zhang4, Sen Jiang4, Xianming Fu1,2,3. 1. Department of Nuerosurgery, Shandong University , Jinan, Shandong Province, P. R. China. 2. Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui Province, P. R. China. 3. Department of Neurosurgery, Anhui Provincial Institute of Stereotactic Neurosurgery , Hefei, Anhui Province, P. R. China. 4. Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University , Hefei, Anhui Province, P. R. China.
Abstract
OBJECTIVE: The effects of microRNAs (miRNAs) have been identified in epilepsy (Ep) in recent years, our research was focused on the functions of miR-494 in Ep and its inner mechanisms. METHODS: The Ep modeled rats induced by lithium chloride-pilocarpine were treated with agomir-miR-494 or RIPK1-siRNA. The pathology of rat hippocampal tissues was observed. Expression of miR-494, receptor-interacting protein kinase 1 (RIPK1) and nuclear factor-kappaB (NF-κB) p65 was assessed by RT-qPCR and Western blot analysis. The hippocampal neurons of epileptic rats were successfully modeled, which were transfected with miR-494 mimics or RIPK1-siRNA to determine neurons' proliferation ability and cell apoptosis. The target relation between miR-494 and RIPK1 was measured by bioinformatics website and dual luciferase gene reporter assay. RESULTS: The expression of miR-494 was reduced, while the expression of RIPK1 and NF-κB p65 was amplified in hippocampus of Ep rats. Elevated miR-494 repressed the expression of RIPK1 to ameliorate the hippocampal neuron injury, accelerate neuronal proliferation, and restrain neuronal apoptosis via inactivating the NF-κB signaling pathway, causing a deceleration of Ep development. Furthermore, amplified RIPK1 was able to reverse the amelioration of neuronal injury in Ep rats which was contributed by upregulated miR-494. CONCLUSION: We found in this study that elevated miR-494 repressed RIPK1, causing an inactivation of the NF-κB signaling pathway and acceleration of cell proliferation, and suppression of apoptosis of hippocampal neurons in Ep rats, thereby attenuating the neuron injury and Ep development. Our research may provide novel targets for the therapy of Ep.
OBJECTIVE: The effects of microRNAs (miRNAs) have been identified in epilepsy (Ep) in recent years, our research was focused on the functions of miR-494 in Ep and its inner mechanisms. METHODS: The Ep modeled rats induced by lithium chloride-pilocarpine were treated with agomir-miR-494 or RIPK1-siRNA. The pathology of rat hippocampal tissues was observed. Expression of miR-494, receptor-interacting protein kinase 1 (RIPK1) and nuclear factor-kappaB (NF-κB) p65 was assessed by RT-qPCR and Western blot analysis. The hippocampal neurons of epilepticrats were successfully modeled, which were transfected with miR-494 mimics or RIPK1-siRNA to determine neurons' proliferation ability and cell apoptosis. The target relation between miR-494 and RIPK1 was measured by bioinformatics website and dual luciferase gene reporter assay. RESULTS: The expression of miR-494 was reduced, while the expression of RIPK1 and NF-κB p65 was amplified in hippocampus of Eprats. Elevated miR-494 repressed the expression of RIPK1 to ameliorate the hippocampal neuron injury, accelerate neuronal proliferation, and restrain neuronal apoptosis via inactivating the NF-κB signaling pathway, causing a deceleration of Ep development. Furthermore, amplified RIPK1 was able to reverse the amelioration of neuronal injury in Eprats which was contributed by upregulated miR-494. CONCLUSION: We found in this study that elevated miR-494 repressed RIPK1, causing an inactivation of the NF-κB signaling pathway and acceleration of cell proliferation, and suppression of apoptosis of hippocampal neurons in Eprats, thereby attenuating the neuron injury and Ep development. Our research may provide novel targets for the therapy of Ep.
Entities:
Keywords:
Epilepsy; MicroRNA-494; apoptosis; nuclear factor-kappaB signaling pathway; proliferation; rat hippocampal neuron injury; receptor-interacting protein kinase 1