MicroRNA‑124 improves functional recovery and suppresses Bax‑dependent apoptosis in rats following spinal cord injury

Xu,Zhongyang; Zhang,Kefeng; Wang,Qian; Zheng,Yanping

doi:10.3892/mmr.2019.9904

MicroRNA‑124 improves functional recovery and suppresses Bax‑dependent apoptosis in rats following spinal cord injury

Authors:
- Zhongyang Xu
- Kefeng Zhang
- Qian Wang
- Yanping Zheng
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Affiliations: Department of Orthopedics, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Orthopedics, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: January 28, 2019 https://doi.org/10.3892/mmr.2019.9904
Pages: 2551-2560
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Spinal cord injury (SCI) induces aberrant expression of microRNAs (miRNAs), causing various secondary injury responses, including inflammation, apoptosis and oxidative stress. However, the mechanisms underlying miRNA‑mediated apoptosis have not been fully elucidated. In the present study, a rat SCI model was established and a miRNA microarray was analyzed to detect miRNA expression profiles at different times post‑SCI. The Basso, Beattie and Bresnahan score, cresyl violet staining and terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling staining were used to evaluate locomotor activity, lesion volume and neuronal cell apoptosis, respectively, at different time points post‑SCI. It was observed that numerous miRNAs were altered at 14 days post‑SCI and miR‑124 was one of the most notably downregulated miRNAs. The present results demonstrated that overexpression of miR‑124 by agomir‑124 improves functional recovery, decreases lesion size and suppresses neuronal cell apoptosis in a rat SCI model. Luciferase reporter assay demonstrated that miR‑124 inhibited apoptosis regulator BAX (Bax) expression, a key molecule in the activation of the mitochondrial apoptotic pathway, by targeting its 3'‑untranslated region in BV‑2 cells. Furthermore, restoration of Bax by pc‑DNA‑Bax inhibits the protective effect of miR‑124 in H2O2‑treated BV‑2 cells. Notably, the present results demonstrated that miR‑124 may block the mitochondrial apoptotic pathway by inhibiting Bax, cleaved‑caspase‑9 and cleaved‑caspase‑3 expression in rats following SCI. Collectively, the present results suggested that miR‑124 may improve functional recovery and supress neuronal cell apoptosis by blocking the mitochondrial apoptotic pathway in SCI rats, suggesting that miR‑124 may serve as a potential therapeutic target in SCI treatment.

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