Circular RNA circ_DROSHA alleviates the neural damage in a cell model of temporal lobe epilepsy through regulating miR-106b-5p/MEF2C axis |
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| Institution: | 1. Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China;2. Beijing Key Laboratory of Neuromodulation, Beijing Municipal Science and Technology Commission, Beijing 100050, China;3. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;4. Department of Neurology, University of Florida, Florida 32607, USA;5. Department of Neurosurgery, Beijing Children''s Hospital, Capital Medical University, Beijing 100045, China;1. Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea;2. Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu, Korea;3. Department of Physiology, School of Medicine, Kyungpook National University Daegu, Daegu, Korea;4. Department of Dental Hygiene, Dong-Eui University, Busan, Korea;1. Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea;2. Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea;3. Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea;1. Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China;2. Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China |
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| Abstract: | Temporal lobe epilepsy (TLE) is the most prevalent form of acquired epilepsy. Circular RNAs (circRNAs) have recently been highlighted as important regulators in TLE. Nevertheless, the role and mechanism of circRNA Drosha ribonuclease III (circ_DROSHA) in TLE pathogenesis are still unknown. Magnesium-free extracellular solution was used to establish the TLE cell model. The levels of circ_DROSHA, myocyte-specific enhancer factor 2C (MEF2C) and miR-106b-5p were determined by qRT-PCR and western blot. Cell proliferation was detected by the Cell Counting-8 Kit (CCK-8) assay, and cell apoptosis was measured by flow cytometry. Targeted relationships among circ_DROSHA, miR-106b-5p and MEF2C were confirmed by a dual-luciferase reporter or RNA immunoprecipitation (RIP) assay. Our data showed that circ_DROSHA was down-regulated in the serum samples of TLE patients and the TLE cell model. Circ_DROSHA up-regulation alleviated the cytotoxicity of the TLE cell model by enhancing cell proliferation and repressing cell apoptosis. Circ_DROSHA directly bound to miR-106b-5p. Moreover, miR-106b-5p represented a downstream effector of circ_DROSHA function. MEF2C was a direct target of miR-106b-5p, and miR-106b-5p knockdown relieved magnesium-free treatment-induced cell injury by up-regulating MEF2C. Furthermore, circ_DROSHA regulated MEF2C expression via sponging miR-106b-5p. Our study suggested that the enforced expression of circ_DROSHA alleviated the cell damage of the TLE cell model at least in part through the regulation of the miR-106b-5p/MEF2C axis. |
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