CircRNA_01477 influences axonal growth via regulating miR-3075/FosB/ Stat3 axis
CircRNA_01477 influences axonal growth via regulating miR-3075/FosB/ Stat3 axis
复制标题
DOI：
10.1016/j.expneurol.2021.113905
复制
发表时间：
2021-10-28
影响因子：
5.3
通讯作者：
Liu, Mei
中科院分区：
文献类型：
--
作者：
Qian, Xiaowei;Lin, Ge;Liu, Mei
环状RNA（circRNA）对于神经系统的发育和再生很重要。我们研究了脊髓损伤诱导的 circRNA 的差异表达谱，并报道 circRNA_01477 促进大鼠损伤后脊髓星形胶质细胞的增殖和迁移。在本研究中，我们进一步阐明了circRNA_01477在神经元中的功能和可能的作用机制。荧光原位杂交分析显示circRNA_01477主要定位于神经元细胞质中。 circRNA_01477 的敲低显着增加了轴突长度。使用 RNA 测序研究了 circRNA_01477/microRNA (miRNA)/信使 RNA (mRNA) 相互作用网络。 circRNA_01477 耗尽后，miRNA-3075 显示出显着增加，并且 miRNA-3075 的过表达或其靶基因 FosB 的下调显着促进轴突生长。荧光素酶报告基因检测显示，miRNA-3075可以直接结合FosB的3'UTR并负向调节FosB转录。 circRNA_01477 和 miR-3075 的双重沉默表明，miR-3075 抑制可以挽救 siCircRNA_01477 引起的轴突长度增加。最后，我们验证了大鼠脊髓神经元中 FosB 蛋白耗尽后 Stat3 通路被激活，而 NF-kappa B 通路没有改变。总之，我们的研究首次报道了 circRNA_01477 通过调节 miRNA-3075/FosB/Stat3 轴充当 miRNA 海绵，从而促进轴突生长。
Circular RNAs (circRNAs) are important for the development and regeneration of the nervous system. We investigated the differential expression profiles of circRNA induced by spinal cord injury and reported that circRNA_01477 facilitates spinal astrocyte proliferation and migration after injury in rats. In this study, we further clarified the function and possible mechanism of action of circRNA_01477 in neurons. Fluorescence in situ hybridization assay revealed that circRNA_01477 is mainly localized in the neuronal cytoplasm. Knockdown of circRNA_01477 significantly increased axonal length. The circRNA_01477/microRNAs (miRNA)/messenger RNA (mRNA) interaction network was investigated using RNA sequencing. miRNA-3075 showed a remarkable increase after circRNA_01477 depletion, and either overexpression of miRNA-3075 or downregulation of its target gene FosB significantly promoted axonal growth. Luciferase reporter assay showed that miRNA-3075 could directly bind to the 3'UTR of FosB and negatively regulated FosB transcription. Dual silencing of circRNA_01477 and miR-3075 revealed that miR-3075 inhibition rescued the increased axon length caused by siCircRNA_01477. Finally, we verified that the Stat3 pathway was activated after FosB protein depletion in rat spinal neurons, while the NF-kappa B pathway was not altered. In summary, our study is the first to report that circRNA_01477 contributes to axon growth by functioning as miRNA sponge by regulating the miRNA-3075/ FosB/Stat3 axis.