Inhibition of microRNA-34 a alleviates spinal cord injury through regulating anti-apoptotic Bcl-2 protein in rats

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2016)

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Abstract
Spinal cord injury (SCI) is a severe health problem, whichcauses lifelong disability for patients. The pathophysiological mechanisms of SCI remain unclear. A large number of experiments show that dysregulation of microRNAs (miRNAs) has been found following SCI. The study aimed to investigate the potential role and underlying mechanism of miR-34a following SCI in vivo and in vitro. We firstly downloaded SCI gene expression data GSE19890 from GEO (Gene Expression Omnibus), and miRNAs associated with SCI were screened in the SCI model rat. Then, the effects of miRNA were assessed by silencing and over-expressing the miRNA in vitro and in vivo. In addition, the regulation of Bcl-2 by miR-34a was evaluated by quantitative real-time RT-PCR (qRT-PCR), western blot and luciferase reporter assays. A total of 43 differentially expressed miRNAs were identified. MiR-34a wasone of the most significantly upregulated in SCI group comparing with sham group, and its expression was validated in SCI model rat. Function assays showed that inhibition of miR-34a improved locomotor function and SCI recovery attenuated tissue damage and decreased apoptotic cell in SCI model rat, while overexpression of miR-34a had an opposite result. Subsequently, in a SCI cell model (BV-2 cells treated with H2O2), we found that the level of miR-34a was also upregulated in a dose-dependent manner. Importantly, downregulation of miR-34a could restore the reduction of cell viability and inhibited cell apoptosis induced by H2O2 in murine BV-2 cells. In addition, anti-apoptosis genes Bcl2, an important regulator of apoptosis, was identified as a direct target of miR-34a. Our present findings suggest that downregulation of miR-34a has a protection effect in SCI by inhibiting cell apoptosisvia targeting Bcl-2. Our data indicate that miR-34a may serve as anovel potential target for SCI diagnosis and therapy.
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Key words
Spinal cord injury, apoptosis, microRNA-34a, Bcl-2
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