Qian Xiaowei, Zhang Wei, Kong Dexia, Huang Chenyi, Liu Yan, Liu Mei, Chen Hongjian, Wu Ronghua
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Faculty of Health Science, Nantong University, Nantong, China.
J Biochem Mol Toxicol. 2025 Aug;39(8):e70404. doi: 10.1002/jbt.70404.
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.
环状RNA（circRNAs）是一类内源性非编码RNA，在各种生理和病理过程中发挥着关键作用。本研究旨在探讨circRNA_26782在脊髓神经元中的作用及其潜在机制。我们分析了脊髓损伤大鼠模型中circRNAs的差异表达谱，并确定circRNA_26782表达下调。荧光原位杂交分析表明，circRNA_26782主要位于神经元细胞质中。敲低circRNA_26782可显著增加轴突长度。RNA测序确定miR-19b-2-5p是circRNA_26782缺失后上调的关键miRNA。过表达miR-19b-2-5p或下调其靶基因Rab1b均可显著增强轴突生长。circRNA_与其共沉默26782和miR-19b-2-5p表明，抑制miR-19b-2-5p可挽救circRNA_26782敲低诱导的轴突长度增加。此外，在大鼠脊髓神经元中，敲低circRNA_26782、过表达miR-19b-2-5p或下调Rab1b均可抑制自噬途径。本研究首次证明，circRNA_26782通过miR-19b-2-5p/Rab1b轴抑制自噬途径来促进轴突生长。这些发现为调节轴突生长的分子机制提供了新的见解，并可能为脊髓损伤的治疗策略提供依据。
