VEGFB-EGFP and circAnks1a-EGFP were used for overexpression of gene
Vegfb and circAnks1a
. AAV-EGFP and Cre-mCherry viruses were used for control.
The viruses used in this article are in the table below
|
Custome-Made AAVs |
AAV-hSyn-circAnks1a-nEF1α-EGFP
AAV-VEGFB-EGFP |
|
CRE Recombinase |
AAV-Cre-mCherry |
|
Control |
AAV-EGFP |
Pub Date: 2019-09-11,
DOI: 10.1038/s41467-019-12049-0，
Email: [email protected]
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 & Wen-Jun Xin
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.
Fig1. Intrathecal injection of VEGFB siRNA significantly decreased the VEGFB mRNA (a) and protein (b) expression.
In the study, the authors showed that a spinal cord-specific circRNA, circAnks1a, promoted the translocation of the transcription factor YBX1 into the nucleus. Furthermore, nuclear circAnks1a facilitated the interaction of YBX1 and the
Vegfb promoter via specific RNA–DNA interaction following nerve injury. Cytoplasmic circAnks1a also served as a miRNA sponge for miR-324-3p and enhanced VEGFB mRNA translation. The upregulation of VEGFB excited the dorsal horn neurons and contributed to pain behavior induced by nerve injury. These findings reveal a novel mechanism and identify specific targets for the treatment of neuropathic pain.
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