1. A sensory neuron-specific long non-coding RNA reduces neuropathic pain by rescuing KCNN1 expression.
- Author
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Wang, Bing, Ma, Longfei, Guo, Xinying, Du, Shibin, Feng, Xiaozhou, Liang, Yingping, Govindarajalu, Gokulapriya, Wu, Shaogen, Liu, Tong, Li, Hong, Patel, Shivam, Bekker, Alex, Hu, Huijuan, and Tao, Yuan-Xiang
- Subjects
LINCRNA ,GENE expression ,NEURALGIA ,CALCIUM-dependent potassium channels ,DORSAL root ganglia ,SCIATIC nerve injuries - Abstract
Nerve injury to peripheral somatosensory system causes refractory neuropathic pain. Maladaptive changes of gene expression in primary sensory neurons are considered molecular basis of this disorder. Long non-coding RNAs (lncRNAs) are key regulators of gene transcription; however, their significance in neuropathic pain remains largely elusive.Here, we reported a novel lncRNA, named sensory neuron-specific lncRNA (SS-lncRNA), for its expression exclusively in dorsal root ganglion (DRG) and trigeminal ganglion. SS-lncRNA was predominantly expressed in small DRG neurons and significantly downregulated due to a reduction of early B cell transcription factor 1 in injured DRG after nerve injury. Rescuing this downregulation reversed a decrease of the calcium-activated potassium channel subfamily N member 1 (KCNN1) in injured DRG and alleviated nerve injury-induced nociceptive hypersensitivity. Conversely, DRG downregulation of SS-lncRNA reduced the expression of KCNN1, decreased total potassium currents and afterhyperpolarization currents and increased excitability in DRG neurons and produced neuropathic pain symptoms.Mechanistically, downregulated SS-lncRNA resulted in the reductions of its binding to Kcnn1 promoter and heterogeneous nuclear ribonucleoprotein M (hnRNPM), consequent recruitment of less hnRNPM to the Kcnn1 promoter and silence of Kcnn1 gene transcription in injured DRG.These findings indicate that SS-lncRNA may relieve neuropathic pain through hnRNPM-mediated KCNN1 rescue in injured DRG and offer a novel therapeutic strategy specific for this disorder. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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