Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
Department of Orthopedic Surgery, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, 200233, China.
Cell Death Dis. 2019 Oct 17;10(11):787. doi: 10.1038/s41419-019-2027-x.
Accumulating evidence suggests that circular RNAs (circRNAs) are abundant and play critical roles in the nervous system. However, their functions in axon regeneration after neuronal injury are unclear. Due to its robust regeneration capacity, peripheral nervous system is ideal for seeking the regulatory circRNAs in axon regeneration. In the present work, we obtained an expression profile of circRNAs in dorsal root ganglions (DRGs) after rat sciatic nerve crush injury by RNA sequencing (RNA-Seq) and found the expression level of circ-Spidr was obviously increased using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, circ-Spidr was proved to be a circular RNA enriched in the cytoplasm of DRG neurons. Through in vitro and in vivo experiments, we determined that down-regulation of circ-Spidr could suppress axon regeneration of DRG neurons after sciatic nerve injury partially through modulating PI3K-Akt signaling pathway. Together, our results reveal a crucial role for circRNAs in regulating axon regeneration after neuronal injury which may further serve as a potential therapeutic avenue for neuronal injury repair.
越来越多的证据表明，环状 RNA（circRNAs）丰富存在并在神经系统中发挥关键作用。然而，它们在神经元损伤后的轴突再生中的功能尚不清楚。由于外周神经系统具有强大的再生能力，因此非常适合寻找轴突再生中的调节 circRNAs。在本研究中，我们通过 RNA 测序（RNA-Seq）获得了大鼠坐骨神经挤压损伤后背根神经节（DRG）中 circRNAs 的表达谱，并通过实时定量聚合酶链反应（qRT-PCR）发现 circ-Spidr 的表达水平明显升高。此外，circ-Spidr 被证明是一种在 DRG 神经元细胞质中富集的环状 RNA。通过体外和体内实验，我们确定下调 circ-Spidr 可以部分通过调节 PI3K-Akt 信号通路来抑制坐骨神经损伤后 DRG 神经元的轴突再生。总之，我们的研究结果揭示了 circRNAs 在调节神经元损伤后轴突再生中的重要作用，这可能为神经元损伤修复提供新的治疗途径。
