Down-regulated miR-10a protects against spinal cord injury by up-regulating SIRT1

Abstract

Abstract Background: Spinal cord injury (SCI) is a sensory and motor deficit that greatly reduces patients’ standard of living. MicroRNAs (miRNAs) are essential modulators of gene expression and are associated with various pathological processes, including SCI. This investigation aimed to elucidate miR-10a activity in SCI and its potential interaction with SIRT1, a known inflammation and cell survivalregulator. Methods: Lentiviral vectors were used to knock down miR-10a in SCI rats. The locomotion scale called Basso, Beattie, and Bresnahan was utilized to assess SCI rats' hindlimbs' functional recovery. PC12 cells were stimulated by lipopolysaccharide (LPS) to establish an in-vitro SCI model. qRT-PCR was carried out to elucidate miR-10a levels in the spinal cord tissues and PC12 cells. The interaction of miR-10a with SIRT1 was elucidated via luciferase reporter analysis. Immunohistochemistry and western blot assessed SIRT1 protein expression. Cell viability was elucidated via MTT analysis, and an ELISA assay was carried out to investigate inflammatory factors. Results: This investigation indicated upregulated miR-10a and reduced SIRT1 expression in the SCI rats’ tissues.miR-10a knockdown in SCI rats improved motor function recovery, increased neuronal survival, and reduced levels of inflammatory cytokines. Luciferase reporter assays confirmed that miR-10adirectly targets SIRT1. In PC12 cells, downregulation of miR-10a increased SIRT1 expression, enhanced cell viability, and reduced inflammatory factor levels afterLPS stimulation. Conversely, SIRT1 knockdown inhibited the protective effects of downregulated miR-10a on cell viability and inflammatory responses. Conclusions: The resultssuggest that miR-10a downregulation protects against SCI by upregulating SIRT1 expression, improving functional recovery, and reducing inflammation. Targeting the miR-10a/SIRT1 axis is a promising strategy for SCItreatment.