CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain
CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain
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脊髓中的 CircAnks1a 调节啮齿动物神经性疼痛模型的超敏反应
DOI：
10.1038/s41467-019-12049-0
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发表时间：
2019-09-11
影响因子：
16.6
通讯作者：
Xin, Wen-Jun
中科院分区：
文献类型：
--
作者：
Zhang, Su-Bo;Lin, Su-Yan;Xin, Wen-Jun
环状RNA是非编码RNA，并且在CNS中富集。啮齿类动物脊髓背角神经元在神经损伤后引起痛样过敏。在这里，我们表明，脊神经结扎与脊髓背角神经元，在细胞质和细胞核中的circAnks 1a的表达增加。siRNA下调circAnks 1a可减弱神经损伤诱导的疼痛样行为在细胞质中，我们发现circAnks 1a促进转录因子YBX 1和转运蛋白-1之间的相互作用，从而促进YBX 1的核转位。在细胞核中，circAnks 1a直接与Vegfb启动子结合，增加YBX 1向Vegfb启动子的募集，从而促进转录。此外，细胞质circAnks 1a在miR-324- 3 p介导的VEGFB表达的转录后调节中充当miRNA海绵。VEGFB的上调有助于增加背角神经元的兴奋性和神经损伤诱导的疼痛行为。我们认为circAnks 1a和VEGFB是神经性疼痛的调节因子。
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 theVegfbpromoter, increases YBX1 recruitment to theVegfbpromoter, 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.