{"title":"组蛋白去甲基化酶KDM6B通过染色质环的形成增加PDGFRA的表达，从而促进胶质瘤细胞的增殖。","authors":"Aixia Sui, Xiaoqiang Guo","doi":"10.1080/01616412.2025.2480326","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Changes in gene expression pattern play an essential role in promoting the process of cancer. For example, platelet-derived growth factor receptor alpha (<i>PDGFRA</i>) is overexpressed in many cancers, including gliomas. Abnormal histone methylation is a typical characteristics of glioma, and our previous studies have shown that histone lysine demethylase 6B (KDM6B) is involved in glioma development by regulating the expression of specific oncogenes. In this study, the regulatory effect and underlying mechanism of KDM6B on <i>PDGFRA</i> expression were investigated.</p><p><strong>Methods: </strong>The expression information of KDM6B and <i>PDGFRA</i> in patients with glioma was analyzed in GEPIA database. The expression or activity of KDM6B was regulated with CRISPR interference/activation (CRISPRi/a) assays, gene knockdown and specific inhibitor. Cell proliferation was determined using cell counting kit assay. Chromatin immunoprecipitation assay (ChIP) and ChIP-loop assays were used to determine the H3K27me3 status in the <i>PDGFRA</i> promoter and DNA-DNA interactions mediated by KDM6B.</p><p><strong>Results: </strong>The expression of KDM6B and <i>PDGFRA</i> expression is positively correlated in gliomas. CRISPRi/a assays indicated that KDM6B has a positive regulatory role in <i>PDGFRA</i> expression in glioma cells and can promote glioma cell proliferation. KDM6B knockdown and inhibitor assays further proved that KDM6B promotes <i>PDGFRA</i> expression. ChIP assays indicated KDM6B reduces H3K27me3 level in the <i>PDGFRA</i> promoter. The ChIP-loop assays showed KDM6B increases the formation of chromatin loops, which facilitates the proximity of enhancer and promoter.</p><p><strong>Conclusion: </strong>This study reveals a new epigenetic mechanism of <i>PDGFRA</i> overexpression in glioma cells, that is, KDM6B catalyzes the demethylation of H3K27me3 and induces chromatin loop formation to activate <i>PDGFRA</i> expression. This study is of great significance for the understanding of glioma development and the application of new treatment strategies, such as radiation therapy combined with epigenetic therapy.</p>","PeriodicalId":19131,"journal":{"name":"Neurological Research","volume":" ","pages":"1-9"},"PeriodicalIF":1.7000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Histone demethylase KDM6B promotes glioma cell proliferation by increasing <i>PDGFRA</i> expression via chromatin loop formation.\",\"authors\":\"Aixia Sui, Xiaoqiang Guo\",\"doi\":\"10.1080/01616412.2025.2480326\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Changes in gene expression pattern play an essential role in promoting the process of cancer. For example, platelet-derived growth factor receptor alpha (<i>PDGFRA</i>) is overexpressed in many cancers, including gliomas. Abnormal histone methylation is a typical characteristics of glioma, and our previous studies have shown that histone lysine demethylase 6B (KDM6B) is involved in glioma development by regulating the expression of specific oncogenes. In this study, the regulatory effect and underlying mechanism of KDM6B on <i>PDGFRA</i> expression were investigated.</p><p><strong>Methods: </strong>The expression information of KDM6B and <i>PDGFRA</i> in patients with glioma was analyzed in GEPIA database. The expression or activity of KDM6B was regulated with CRISPR interference/activation (CRISPRi/a) assays, gene knockdown and specific inhibitor. Cell proliferation was determined using cell counting kit assay. Chromatin immunoprecipitation assay (ChIP) and ChIP-loop assays were used to determine the H3K27me3 status in the <i>PDGFRA</i> promoter and DNA-DNA interactions mediated by KDM6B.</p><p><strong>Results: </strong>The expression of KDM6B and <i>PDGFRA</i> expression is positively correlated in gliomas. CRISPRi/a assays indicated that KDM6B has a positive regulatory role in <i>PDGFRA</i> expression in glioma cells and can promote glioma cell proliferation. KDM6B knockdown and inhibitor assays further proved that KDM6B promotes <i>PDGFRA</i> expression. ChIP assays indicated KDM6B reduces H3K27me3 level in the <i>PDGFRA</i> promoter. The ChIP-loop assays showed KDM6B increases the formation of chromatin loops, which facilitates the proximity of enhancer and promoter.</p><p><strong>Conclusion: </strong>This study reveals a new epigenetic mechanism of <i>PDGFRA</i> overexpression in glioma cells, that is, KDM6B catalyzes the demethylation of H3K27me3 and induces chromatin loop formation to activate <i>PDGFRA</i> expression. This study is of great significance for the understanding of glioma development and the application of new treatment strategies, such as radiation therapy combined with epigenetic therapy.</p>\",\"PeriodicalId\":19131,\"journal\":{\"name\":\"Neurological Research\",\"volume\":\" \",\"pages\":\"1-9\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-03-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurological Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/01616412.2025.2480326\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurological Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01616412.2025.2480326","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Histone demethylase KDM6B promotes glioma cell proliferation by increasing PDGFRA expression via chromatin loop formation.
Objectives: Changes in gene expression pattern play an essential role in promoting the process of cancer. For example, platelet-derived growth factor receptor alpha (PDGFRA) is overexpressed in many cancers, including gliomas. Abnormal histone methylation is a typical characteristics of glioma, and our previous studies have shown that histone lysine demethylase 6B (KDM6B) is involved in glioma development by regulating the expression of specific oncogenes. In this study, the regulatory effect and underlying mechanism of KDM6B on PDGFRA expression were investigated.
Methods: The expression information of KDM6B and PDGFRA in patients with glioma was analyzed in GEPIA database. The expression or activity of KDM6B was regulated with CRISPR interference/activation (CRISPRi/a) assays, gene knockdown and specific inhibitor. Cell proliferation was determined using cell counting kit assay. Chromatin immunoprecipitation assay (ChIP) and ChIP-loop assays were used to determine the H3K27me3 status in the PDGFRA promoter and DNA-DNA interactions mediated by KDM6B.
Results: The expression of KDM6B and PDGFRA expression is positively correlated in gliomas. CRISPRi/a assays indicated that KDM6B has a positive regulatory role in PDGFRA expression in glioma cells and can promote glioma cell proliferation. KDM6B knockdown and inhibitor assays further proved that KDM6B promotes PDGFRA expression. ChIP assays indicated KDM6B reduces H3K27me3 level in the PDGFRA promoter. The ChIP-loop assays showed KDM6B increases the formation of chromatin loops, which facilitates the proximity of enhancer and promoter.
Conclusion: This study reveals a new epigenetic mechanism of PDGFRA overexpression in glioma cells, that is, KDM6B catalyzes the demethylation of H3K27me3 and induces chromatin loop formation to activate PDGFRA expression. This study is of great significance for the understanding of glioma development and the application of new treatment strategies, such as radiation therapy combined with epigenetic therapy.
期刊介绍：
Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields.
The scope of the journal includes:
•Stem cell applications
•Molecular neuroscience
•Neuropharmacology
•Neuroradiology
•Neurochemistry
•Biomathematical models
•Endovascular neurosurgery
•Innovation in neurosurgery.
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