microRNA‐125b and its downstream Smurf1/KLF2/ATF2 axis as important promoters on neurological function recovery in rats with spinal cord injury

The purpose of this study is to investigate the role of microRNA‐125b (miR‐125b) and its mechanism in spinal cord injury (SCI) by targeting Smurf1. After loss‐ and gain‐function approaches were conducted in SCI rat models and neural stem cells (NSCs) isolated from foetal rats, the Basso‐Beattie‐Bresnahan (BBB) score was calculated, and related protein expression was determined by Western blot analysis and cell apoptosis by TUNEL staining. NSC viability was detected by CCK‐8, migration abilities by Transwell assay and apoptosis by flow cytometry. The relationship between miR‐125b, Smurf1 and KLF2 was evaluated by dual‐luciferase reporter gene experiments, Co‐IP and in vivo ubiquitin modification assays. Inhibition of miR‐125b and KLF2 and the up‐regulation of Smurf1 and ATF2 were observed in SCI rats. BBB scores were elevated, the expression of Nestin, NeuN, GFAP, NF‐200 and Bcl‐2 protein was enhanced but that of Bax protein was reduced, and cell apoptosis was inhibited in SCI rats after up‐regulating miR‐125b or silencing ATF2. Smurf1 was a target gene of miR‐125b, which promoted KLF2 degradation through its E3 ubiquitin ligase function, and KLF2 repressed the expression of ATF2 in NSCs. The results in vivo were replicated in vitro. miR‐125b overexpression promotes neurological function recovery after SCI.