Silencing of miR-324-5p alleviates rat spinal cord injury by Sirt1.
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| Abstract |
MicroRNAs (miRNAs) are implicated in the pathogenesis of spinal cord injury (SCI) as primary regulators. Previous studies have reported that miR-324-5p is involved in the modulation of neural injury, while the underlying mechanisms of miR-324-5p in SCI remain unclear. In a SCI rat model, miR-324-5p was significantly upregulated in the spinal cord tissues after SCI. Downregulation of miR-324-5p via injection of adeno-associated viruses (AAV) expressing miR-324-5p inhibitor relieved animal motor deficits and pathological changes in the tissues. Furthermore, downregulation of miR-324-5p significantly altered the expression of genes regulating neural growth, apoptosis, and the inflammatory and antioxidant response, which are implicated in SCI pathogenesis. In a H2O2-induced cell injury model, miR-324-5p silencing rescued the elevated apoptosis of PC12 cells. Finally, miR-324-5p directly targeted the 3'-untranslated region of NAD-dependent protein deacetylase sirtuin-1 (Sirt1) and negatively regulated the levels of Sirt1, an anti-inflammatory protein involved in SCI. Silencing of Sirt1 aggravated SCI and rescued the effects of miR-324-5p downregulation in rats. Overall, our findings indicated that silencing of miR-324-5p alleviates the loss of animal locomotion and concurrently mediates several degenerative processes relevant to the pathogenesis of SCI by Sirt1, which may provide clues for SCI treatment.
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| Authors | Chuanbao Wang, Xiuli Guo, Ying Wang, Hai Wang |
| Journal | Neuroscience research (Neurosci Res) Vol. 173 Pg. 34-43 (Dec 2021) ISSN: 1872-8111 [Electronic] Ireland |
| PMID | 34051279 (Publication Type: Journal Article) |
| Copyright | Copyright © 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved. |
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