MicroRNA-135a-5p promotes the functional recovery of spinal cord injury by targeting SP1 and ROCK

Emerging evidence indicates that microRNAs play a pivotal?role in neural remodeling after spinal cord injury (SCI). This?study aimed to investigate the mechanisms of miR-135a-5p?in regulating the functional recovery of SCI by impacting its?target genes and downstream signaling. The gene transfection?assay and luciferase reporter assay confirmed the target relationship between miR-135a-5p and its target genes (specificity?protein 1 [SP1] and Rho-associated kinase [ROCK]1/2). By?establishing the H2O2-induced injury model, miR-135a-5p?transfection was found to inhibit the apoptosis of PC12 cells?by downregulating the SP1 gene, which subsequently induced?downregulation of pro-apoptotic proteins (Bax, cleaved caspase-3) and upregulation of anti-apoptotic protein Bcl-2. By?measuring the neurite lengths of PC12 cells, miR-135a-5p?transfection was found to promote axon outgrowth by downregulating the ROCK1/2 gene, which subsequently caused upregulation of phosphate protein kinase B (AKT) and phosphate?glycogen synthase kinase 3b (GSK3b). Use of the rat SCI?models showed that miR-135a-5p could increase the Basso,Beattie, and Bresnahan (BBB) scores, indicating neurological?function recovery. In conclusion, the miR-135a-5p-SP1-Bax/Bcl-2/caspase-3 and miR-135a-5p-ROCK-AKT/GSK3b axes are involved in functional recovery of SCI by regulating neural?apoptosis and axon regeneration, respectively, and thus can be?promising effective therapeutic strategies in SCI.

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