• Neuroscience · Apr 2024

    MiR-10b-5p regulates neuronal autophagy and apoptosis induced by spinal cord injury through UBR7.

    • Shuangmei Liu, Huali Liu, Chunyan Gong, Guiliang Li, Qiaofen Li, Zhipeng Pan, Xiaona He, Zhilv Jiang, Heng Li, and Chunjun Zhang.
    • Department of Rehabilitation Medicine, Qujing No.1 Hospital, Qujing 655000, China.
    • Neuroscience. 2024 Apr 5; 543: 132713-27.

    AbstractThis study aimed to explore the effects of miR-10b-5p on autophagy and apoptosis in neuronal cells after spinal cord injury (SCI) and the molecular mechanism. Bioinformatics was used to analyze the differentially expressed miRNAs. The expression of related genes and proteins were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Cell proliferation was detected by 5-ethynyl-2'-deoxyuridine (EdU), and apoptosis was detected by flow cytometry or terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). Coimmunoprecipitation confirmed the interaction between UBR7 and Wnt1 or Beclin1. Autophagy was detected by the dansylcadaverine (MDC). The Basso Beattie Bresnahan (BBB) score was used to evaluate motor function, and hematoxylin-eosin (H&E) and Nissl staining were used to detect spinal cord tissue repair and neuronal changes. The result shows that the expression of miR-10b-5p was downregulated in the SCI models, and transfection of a miR-10b-5p mimic inhibited neuronal cell apoptosis. MiR-10b-5p negatively regulated the expression of UBR7, and the inhibitory effect of the miR-10b-5p mimic on neuronal cell apoptosis was reversed by overexpressing UBR7. In addition, UBR7 can regulate apoptosis by affecting the Wnt/β-catenin pathway by promoting Wnt1 ubiquitination. Treatment with the miR-10b-5p mimic effectively improved motor function, inhibited neuronal cell apoptosis, and promoted spinal cord tissue repair in SCI rats. Overall, miR-10b-5p can alleviate SCI by downregulating UBR7 expression, inhibiting Wnt/β-catenin signaling pathway ubiquitination to reduce neuronal apoptosis, or inhibiting Beclin 1 ubiquitination to promote autophagy.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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