• Neuroscience · Aug 2023

    LncRNA FTX inhibits ferroptosis of hippocampal neurons displaying epileptiform discharges in vitro through the miR-142-5p/GABPB1 axis.

    • Guoli Zhang, Ying Gao, Lixin Jiang, and Yuhang Zhang.
    • Department of Pediatrics, The Sixth Affiliated Hospital of Harbin Medical University, No.998, Aiying street, Songbei district, Harbin city, Heilongjiang Province 150023, PR China. Electronic address: guoliz0622@163.com.
    • Neuroscience. 2023 Aug 21; 526: 486048-60.

    AbstractEpilepsy is a disabling and drug-refractory neurological disorder. Long non-coding RNAs (lncRNAs) play a vital role in neuronal function and central nervous system development. This study aimed to explore the regulatory mechanism of lncRNA five prime to Xist (FTX) in cell ferroptosis following epilepsy to provide a theoretical foundation for epilepsy management. Hippocampal neurons were isolated from brain tissues of healthy male SD rats, and an in vitro cell model of epilepsy was established using magnesium-free (MGF) induction. Patch-clamp technique was used to determine the action potentials of neurons. Neuronal viability and apoptosis were assessed by CCK-8 assay and flow cytometry. Levels of FTX, miR-142-5p, and GABPB1 were determined by RT-qPCR and Western blot, respectively. The cellular location of FTX was predicted and validated by RNA immunoprecipitation. Dual-luciferase assay verified targeting relationships among FTX, miR-142-5p, and GAPBP1. Levels of ferroptosis indicators and ferroptosis-related proteins were measured using Western blot and corresponding kits. Neuronal ferroptosis and apoptosis increased after MGF induction, and FTX was weakly-expressed in MGF-induced neurons. FTX overexpression attenuated ferroptosis and apoptosis of MGF-induced neurons. miR-142-5p was upregulated after MGF induction and downregulated after FTX overexpression, and FTX targeted miR-142-5p. miR-142-5p overexpression partially negated the inhibitory action of FTX overexpression on ferroptosis of MGF-induced neurons. FTX regulated GABPB1 expression by targeting miR-142-5p. In conclusion, FTX overexpression mitigated ferroptosis of MGF-induced neurons through the miR-142-5p/GABPB1 axis. In conclusion, lncRNA FTX inhibited ferroptosis of MGF-induced rat hippocampal neurons via the miR-142-5p/GABPB1 axis.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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