Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain.

Autor: Zhang ZX; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center and Neuroscience Research Institute, Peking University, Beijing, China., Tian Y; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center and Neuroscience Research Institute, Peking University, Beijing, China.; Key Laboratory for Neuroscience, Ministry of Education of China & National Health Commission of China, Beijing, 100191, China., Li S; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center and Neuroscience Research Institute, Peking University, Beijing, China., Jing HB; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center and Neuroscience Research Institute, Peking University, Beijing, China., Cai J; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center and Neuroscience Research Institute, Peking University, Beijing, China.; Key Laboratory for Neuroscience, Ministry of Education of China & National Health Commission of China, Beijing, 100191, China., Li M; Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, China. liminanesth@bjmu.edu.cn., Xing GG; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center and Neuroscience Research Institute, Peking University, Beijing, China. ggxing@bjmu.edu.cn.; Key Laboratory for Neuroscience, Ministry of Education of China & National Health Commission of China, Beijing, 100191, China. ggxing@bjmu.edu.cn.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2024 Aug 27; Vol. 22 (1), pp. 416. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1186/s12964-024-01797-2
Abstrakt: Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients.
(© 2024. The Author(s).)
Databáze: MEDLINE
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