PuSH - Publication Server of Helmholtz Zentrum München: PRMT2-mediated upregulation of miR-323-3p in sensory neurons promotes trigeminal neuropathic pain by targeting Kv2.1 channels.

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Qi, R.* ; Tao, Y.* ; Wang, S.* ; Zhou, Y.* ; Sun, Y.* ; Jiang, D. ; Huang, Z.* ; Chen, G.* ; Zhao, G.* ; Zhang, Y.* ; Rui, Y.* ; Tao, J.*

PRMT2-mediated upregulation of miR-323-3p in sensory neurons promotes trigeminal neuropathic pain by targeting Kv2.1 channels.

Cell Rep. 44:116028 (2025)

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Herein, we show a molecular pathway driven by an evolutionarily conserved microRNA (miRNA) in sensory neurons to control neuropathic pain. By employing high-throughput sequencing analysis, we find that miRNA-323-3p (miR-323-3p) exhibits the most significant upregulation in injured trigeminal ganglia (TGs). Local inhibition of miR-323-3p in injured TGs suppresses established trigeminal neuropathic pain but has no effect on inflammatory pain. Mechanistically, nerve injury upregulates the protein expression of protein arginine methyltransferase 2 (PRMT2), which promotes asymmetric dimethylation of H3R8, thereby facilitating the binding of the transcription factor forkhead box A2 (FOXA2) to the miR-323-3p promoter and resulting in the upregulation of miR-323-3p expression. Furthermore, the increased miR-323-3p expression induces significant reductions in Kv2.1 protein expression and channel currents, resulting in TG neuronal hyperexcitability. Conversely, the downregulation of miR-323-3p in injured TGs restores the decreased Kv2.1 expression and attenuates nerve-injury-induced mechanical hypersensitivity. The PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons may offer therapeutic targets in neuropathic pain management.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cp: Molecular Biology ; Cp: Neuroscience ; Kv2.1 Potassium Channel ; Prmt2 ; Mir-323-3p ; Neuropathic Pain ; Trigeminal Ganglion Neurons

ISSN (print) / ISBN 2211-1247

e-ISSN 2211-1247

Journal Cell Reports

Quellenangaben Volume: 44, Issue: 8, Article Number: 116028

Publisher Cell Press

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Regenerative Biology and Medicine (IRBM)