1. CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain.
- Author
-
Zhang SB, Lin SY, Liu M, Liu CC, Ding HH, Sun Y, Ma C, Guo RX, Lv YY, Wu SL, Xu T, and Xin WJ
- Subjects
- Animals, Base Sequence, Cell Nucleus metabolism, DNA-Binding Proteins metabolism, Disease Models, Animal, Male, Mice, Inbred C57BL, MicroRNAs metabolism, Neurons metabolism, Promoter Regions, Genetic genetics, Protein Binding, Protein Transport, Rats, Sprague-Dawley, Rodentia, Spinal Cord Dorsal Horn metabolism, Up-Regulation genetics, Vascular Endothelial Growth Factor B metabolism, Hypersensitivity metabolism, Neuralgia genetics, Neuralgia metabolism, RNA, Circular genetics, Spinal Cord metabolism
- Abstract
Circular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus. Downregulation of circAnks1a by siRNA attenuates pain-like behaviour induced by nerve injury. In the cytoplasm, we show that circAnks1a promotes the interaction between transcription factor YBX1 and transportin-1, thus facilitating the nucleus translocation of YBX1. In the nucleus, circAnks1a binds directly to the Vegfb promoter, increases YBX1 recruitment to the Vegfb promoter, thereby facilitating transcription. Furthermore, cytoplasmic circAnks1a acts as a miRNA sponge in miR-324-3p-mediated posttranscriptional regulation of VEGFB expression. The upregulation of VEGFB contributes to increased excitability of dorsal horn neurons and pain behaviour induced by nerve injury. We propose that circAnks1a and VEGFB are regulators of neuropathic pain.
- Published
- 2019
- Full Text
- View/download PDF