MiR‑222-3p reduces neuronal cell apoptosis and alleviates spinal cord injury by inhibiting Bbc3 and Bim. (March 2023)

• Record Type: Journal Article
• Authors: Zhang, Qiangqiang; Li, Gang; Kong, Jundong; Dai, Junyu; Fan, Zhongkai; Li, Jian
• Is Part Of: Neuroscience research. Volume 188(2023)
• Page Start: 39
• Page End: 50
• Publication Date: 2023-03
• Subjects: SCI spinal cord injury -- Bbc3 Bcl-2 binding component 3 -- Bim Bcl-2 interacting mediator of cell death -- C-caspase 3 Cleaved-Caspase 3 -- C-caspase 9 Cleaved-Caspase 9 -- MMP mitochondrial membrane potential -- BBB Basso, Beattie and Bresnahan -- BH3 Bcl-2 homology domain 3 -- RT-qPCR real-time quantitative PCR -- Cyt C Cytochrome c -- PRDM5 PR/SET domain 5 -- UTR untranslated region -- PD Parkinson's disease -- VDAC voltage-dependent anion channel, CCK-8, Cell Counting Kit-8 -- MOMP mitochondrial outer membrane permeabilization; Spinal cord injury -- Neuronal apoptosis -- MiR-222-3p -- Bbc3 -- Bim; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2022.10.008
• Languages: English
• ISSNs: 0168-0102

Abstract

Abstract: Spinal cord injury (SCI) is a severe traumatic event, but without any established effective treatment because of the irreversible neuronal death. Here, we investigated the role of miR-222-3p in neuronal apoptosis following SCI. Rat SCI models and neuron hypoxia models were accordingly established. The Bbc3, Bim, Bcl-2, Bax, cleaved-caspase 3, cleaved-caspase 9, Cytochrome c, and miR-222-3p expression levels were examined by Western blotting and real-time reverse transcription polymerase chain reaction (RT-qPCR). The possible association between miR-222-3p and Bbc3/Bim was analyzed by dual-luciferase assay. The neuron viability was assessed by Cell Counting Kit-8 assay and Nissl's staining. Live cell staining was performed to detect the mitochondrial membrane potential and neuronal apoptosis. Rat locomotor function was assessed using the Basso–Beattie–Bresnahan scores. Cytochrome c was outflowed from the mitochondria after SCI or hypoxia treatment, and Bbc3, Bim, Bax, cleaved-caspase 9, and cleaved-caspase 3 were significantly upregulated, while Bcl-2 and miR-222-3p were decreased remarkably. Meanwhile, neuronal cell viability was significantly inhibited. Treatment of miR-222-3p significantly suppressed the Cytochrome c efflux and neuronal apoptosis and improved neuronal cell viability and motor function in SCI rats. Moreover, we found that Bbc3 and Bim were the direct targets of miR-222-3p. Overall, our data suggest that miR-222-3p could alleviate the mitochondrial pathway-mediated apoptosis and motor dysfunction in rats after SCI by targeting Bbc3 and Bim. Highlights: Massive neuronal apoptosis is the main cause of dysfunction after SCI. The Bbc3, Bim and miR-222-3p were played an important role in neuronal apoptosis after SCI. miR-222-3p can directly inhibit the expression of Bbc3 and Bim. Increasing miR-222-3p after SCI can inhibit neuronal apoptosis and promote functional recovery.