• Neuroscience · Jul 2023

    The RNA Binding Protein HuR Promotes Neuronal Apoptosis in Rats with Spinal Cord Injury via the HDAC1/RAD21 Axis.

    • Changsheng Wang, Xiaobo Zhang, Xitian Zhu, Rongsheng Chen, and Nancheng Lian.
    • Department of Orthopedics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350212, PR China; Department of Spinal Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, PR China. Electronic address: wangchangsheng085@163.com.
    • Neuroscience. 2023 Jul 1; 522: 109120109-120.

    AbstractThe current research aims to study the regulation of the RNA binding protein HuR on neuronal apoptosis during spinal cord injury (SCI) and its underlying mechanism. SCI rat models were injected with HuR shRNA and/or pcDNA3.1-RAD21, followed by the evaluation of motor function, the degree of SCI, the expression of HuR and RAD21, and neuronal-like apoptosis. The co-localization of HuR-RAD21, RAD21-NeuN, and NeuN-cleaved caspase 3 was measured by immunofluorescence. Additionally, targeting relationships among HuR, HDAC1, and RAD21 were verified by chromatin immunoprecipitation and RNA immunoprecipitation. After transfection, apoptosis of PC12 cells was tested by flow cytometry. Results showed that silencing HuR or up-regulating RAD21 could alleviate SCI and reduce neuronal apoptosis. HuR could combine HDAC1 mRNA, and HDAC1 combined the promoter of RAD21. Further experiments revealed that HuR enhanced HDAC1 expression and reduced RAD21 promoter region acetylation. Overexpression of RAD21 reversed the enhancement in apoptosis of PC12 cells caused by overexpression of HuR. The injection of HuR shRNA in tail vein of SCI rats increased basso, beattie, and bresnahan score, relieved SCI, reduced HuR and HDAC1 expression, elevated RAD21 expression, and decreased neuronal-like apoptosis. However, this result was reversed by co-injection of pcDNA3.1-HDAC1. In conclusion, down-regulation of HuR alleviated SCI and neuronal apoptosis in rats by suppressing HDAC1 expression and promoting RAD21 expression.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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