CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain

Su-Bo Zhang, Su-Yan Lin, Meng Liu, Cui-Cui Liu, Huan-Huan Ding, Yang Sun, Chao Ma (), Rui-Xian Guo, You-You Lv, Shao-Ling Wu, Ting Xu () and Wen-Jun Xin ()
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Su-Bo Zhang: Sun Yat-Sen University
Su-Yan Lin: Sun Yat-Sen University
Meng Liu: Sun Yat-Sen University
Cui-Cui Liu: Sun Yat-Sen University
Huan-Huan Ding: Sun Yat-Sen University
Yang Sun: the Second Affiliated Hospital of Xi’an Medical University
Chao Ma: Sun Yat-Sen University
Rui-Xian Guo: Sun Yat-Sen University
You-You Lv: the Fifth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University
Shao-Ling Wu: Sun Yat-Sen University
Ting Xu: Sun Yat-Sen University
Wen-Jun Xin: Sun Yat-Sen University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12049-0

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