ABSTRACT: Schwann cells (SCs) play an essential role in nerve injury repair. A striking feature of the cellular response to peripheral nerve injury is the proliferation of SCs. Circular (circ)RNAs are enriched in the nervous system and are involved in physiologic and pathologic processes. However, the potential role of circRNAs in SC proliferation post nerve injury remains largely unknown. Using a sciatic nerve crush model, we obtained an expression profiling of circRNAs in injured sciatic nerves in rats by RNA sequencing and bioinformatics analysis, and we further identified a circRNA [circ-ankyrin repeat and in-between Ring finger (IBR) domain containing 1 (Ankib1)] involved in SC proliferation by the transfection of specific small interfering RNAs. Overexpression of circ-Ankib1, which was specifically and highly enriched in SCs, impaired SC proliferation and axon regeneration following sciatic nerve injury. Mechanistically, increased expression of DEx/H-box helicase 9 (DHX9) postinjury might contribute to the down-regulation of circ-Ankib1, which further suppressed cytochrome P450, family 26, subfamily B, polypeptide 1 expression by sponging miR-423-5p, miR-485-5p, and miR-666-3p, leading to the induction of SC proliferation and nerve regeneration. Taken together, our results reveal a crucial role for circRNAs in regulating proliferation of SCs involved in sciatic nerve regeneration; as such, circRNAs may serve as a potential therapeutic avenue for nerve injury repair.-Mao, S., Zhang, S., Zhou, S., Huang, T., Feng, W., Gu, X., Yu, B. A Schwann cell-enriched circular RNA circ-Ankib1 regulates Schwann cell proliferation following peripheral nerve injury.
