CircRNA_26782 Regulates Axonal Growth via Inhibiting the Autophagy Pathway in a Rat Model of Spinal Cord Injury.

Abstract

Circular RNAs (circRNAs), a class of endogenous noncoding RNAs, play crucial roles in various physiological and pathological processes. This study aimed to investigate the role and underlying mechanisms of circRNA_26782 in spinal neurons. We analyzed the differential expression profiles of circRNAs in a rat model of spinal cord injury and identified circRNA_26782 as being downregulated. Fluorescence in situ hybridization assay demonstrated that circRNA_26782 is primarily situated in the neuronal cytoplasm. Knockdown of circRNA_26782 remarkably increased axonal length. RNA sequencing identified miR-19b-2-5p as a key miRNA upregulated following circRNA_26782 depletion. Axonal growth was significantly enhanced by either overexpressing miR-19b-2-5p or downregulating its target gene, Rab1b. Co-silencing of circRNA_26782 and miR-19b-2-5p indicated that miR-19b-2-5p inhibition rescued the increased axon length induced by circRNA_26782 knockdown. Additionally, the autophagy pathway was inhibited upon circRNA_26782 knockdown, miR-19b-2-5p overexpression, or Rab1b downregulation in rat spinal neurons. This study is the first to demonstrate that circRNA_26782 promotes axonal growth by inhibiting the autophagy pathway through the miR-19b-2-5p/Rab1b axis. These findings offer new insights into the molecular mechanisms regulating axonal growth, and potentially informing therapeutic strategies for spinal cord injury.