MiR‐92b‐3p promotes neurite growth and functional recovery via the PTEN/AKT pathway in acute spinal cord injury

Abstract

Emerging evidence indicates that microRNAs play an important role in neural remodeling, including neurite growth, after acute spinal cord injury (ASCI). This study aims to identify the mechanism by which miR‐92b‐3p regulates neurite growth in vivo and in vitro. Adult Sprague–Dawley rats were selected to establish the ASCI model, and the expressions of miR‐92b‐3p and phosphate and tensin homolog deleted on chromosome ten (PTEN) were quantified at different time points. The interaction between miR‐92b‐3p and PTEN was further detected in the PC12 cell line and dual‐luciferase reporter assay. Neurite growth proteins (GAP43 and NF‐200) were assessed by western blotting after miR‐92b‐3p mimics treatment. The PTEN/AKT pathway‐related proteins and their roles in miR‐92b‐3p regulation were also identified using western blotting and immunofluorescence in vitro through LY294002, an AKT inhibitor. The effect of miR‐92b‐3p was further determined in vivo according to the Basso‐Beattie‐Bresnahan (BBB) Scale and GAP43 and NF‐200 expressions. miR‐92b‐3p was downregulated after ASCI, while PTEN showed a simultaneous opposing trend. Overexpression of miR‐92b‐3p downregulated PTEN expression and promoted phosphorylation of AKT, as well as the expression of GAP43 and NF‐200 in PC12 cells. Furthermore, the dual‐luciferase reporter assay revealed that miR‐92b‐3p exerted its effect by targeting PTEN's 3ʹ‐untranslated regions and that this effect could be counteracted by AKT phosphorylation blocker LY294002 through western blotting and immunofluorescence. Moreover, miR‐92b‐3p could also improve the BBB scale as well as GAP43 and NF‐200 expression levels in vivo. Collectively, these results indicate that miR‐92b‐3p promotes neurite growth and functional recovery through the PTEN/AKT pathway in ASCI.