The histone H3 Lys 27 demethylase KDM6B promotes migration and invasion of glioma cells partly by regulating the expression of SNAI1. (March 2019)

• Record Type: Journal Article
• Authors: Sui, Aixia; Xu, Yongbing; Yang, Junjie; Pan, Baogen; Wu, Jiang; Guo, Tao; Shen, Yongqing; Guo, Xiaoqiang
• Is Part Of: Neurochemistry international. Volume 124(2019)
• Page Start: 123
• Page End: 129
• Publication Date: 2019-03
• Subjects: Histone demethylase -- KDM6B -- Glioma -- Migration -- Invasion -- SNAI1; KDM6B Lysine demethylase 6B -- JMJD3 jumonji domain-containing protein 3 -- H3K27me3 histone H3 Lys 27 trimethylation -- CRISPRi CRISPR interference -- CRISPRa CRISPR activation -- qPCR quantitative polymerase chain reaction -- ChIP Chromatin immunoprecipitation -- EMT epithelial-mesenchymal transition; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2019.01.006
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: The histone demethylase KDM6B, also known as jumonji domain-containing protein 3 (JMJD3), is an epigenetic regulator which plays important roles in immune activation, tissue regeneration, cellular senescence and cancer metastasis. But, the role of KDM6B in glioma metastasis is poorly understood. In this study, we achieved transcriptional regulation of KDM6B in glioma cells using CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa). Our results showed that KDM6B promotes the proliferation, migration and invasion of human glioblastoma cells U87 and U251 using CCK8, scratch and transwell assays. Further results indicated that KDM6B increases the expression of SNAI1, a key factor of epithelial-mesenchymal transition (EMT). KDM6B catalyzes the demethylation of histone H3 Lys 27 trimethylation (H3K27me3) in the promoter of SNAI1, which is important for SNAI1 upregulation. Taken together, these findings provide new insight into the mechanism by which KDM6B promotes glioma metastasis. Highlights: The expression regulation of histone demethylase KDM6B was achieved with CRISPRi/CRISPRa assay. KDM6B promoted glioma cell proliferation, migration and invasion. KDM6B increased SNAI1 expression. KDM6B can bind to promoter region of SNAI1 and catalyzing the demethylation of repressive mark H3K27me3.