دورية أكاديمية
Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain
| العنوان: | Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain |
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| المؤلفون: | Zi-Xian Zhang, Yue Tian, Song Li, Hong-Bo Jing, Jie Cai, Min Li, Guo-Gang Xing |
| المصدر: | Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-31 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Cytology |
| مصطلحات موضوعية: | Bone cancer pain, Kv7(KCNQ)/M potassium channels, Transcriptional repression, Histone deacetylase 2, Methyl CpG binding protein 2, Epiregulin, Medicine, Cytology, QH573-671 |
| الوصف: | Abstract 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1478-811X |
| Relation: | https://doaj.org/toc/1478-811X |
| DOI: | 10.1186/s12964-024-01797-2 |
| URL الوصول: | https://doaj.org/article/86cac846465f4ff0a6ecb161acf7ae22 |
| رقم الأكسشن: | edsdoj.86cac846465f4ff0a6ecb161acf7ae22 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1478811X |
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| DOI: | 10.1186/s12964-024-01797-2 |