An investigation into the role of circular RNA in zebrafish spinal cord regeneration with focus on circRNA-miRNA interaction

Zebrafish (Danio rerio) serve as a valuable model for studying spinal cord regeneration due to their remarkable ability to restore the central nervous system (CNS), challenging the long-standing belief that neurons in the adult CNS cannot regenerate. While current knowledge of spinal cord regeneration primarily centers around signaling pathways like the Wingless/Integrated-1 pathway, emerging evidence suggests that circular RNAs (circRNA) also play a critical role in cellular regeneration. Studies in mouse models and human intestinal epithelium have demonstrated the importance of circRNAs in tissue repair, and significant changes in circRNA expression have been observed in zebrafish spinal cord following injury. However, there has been a lack of investigation into what roles circRNAs play in zebrafish spinal cord regeneration. This proposal seeks to fill this research gap by conducting global RNA sequencing to identify the spinal cord injury regenerative circRNA (SCIR-circRNA) that is most differentially expressed before and after spinal cord transection. The role of this SCIR-circRNA in spinal cord regeneration will then be examined through RNAi knockdown experiments to determine whether it promotes or inhibits the regenerative process. Furthermore, the study will focus on SCIR-circRNA and microRNAs (miRNAs) to elucidate their interaction via luciferase assay and RNA pulldown assay. The expected outcomes of this research will contribute to a deeper understanding of the molecular mechanisms underlying spinal cord regeneration and may identify novel therapeutic targets for treating spinal cord injuries.