组蛋白 H3 赖氨酸 27 去甲基化酶 KDM6B 通过调节 SNAI1 的表达促进胶质瘤细胞的迁移和侵袭。
The histone H3 Lys 27 demethylase KDM6B promotes migration and invasion of glioma cells partly by regulating the expression of SNAI1.
机构信息
Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China.
Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China; Graduate School, Hebei Medical University, Shijiazhuang, 050051, Hebei, China.
出版信息
Neurochem Int. 2019 Mar;124:123-129. doi: 10.1016/j.neuint.2019.01.006. Epub 2019 Jan 8.
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.
组蛋白去甲基化酶 KDM6B，也称为 jumonji 结构域包含蛋白 3（JMJD3），是一种表观遗传调节剂，在免疫激活、组织再生、细胞衰老和癌症转移中发挥重要作用。但是，KDM6B 在神经胶质瘤转移中的作用知之甚少。在这项研究中，我们使用 CRISPR 干扰（CRISPRi）和 CRISPR 激活（CRISPRa）在神经胶质瘤细胞中实现了 KDM6B 的转录调控。我们的结果表明，KDM6B 通过 CCK8、划痕和 Transwell 测定促进人胶质母细胞瘤细胞 U87 和 U251 的增殖、迁移和侵袭。进一步的结果表明，KDM6B 增加了上皮-间充质转化（EMT）的关键因子 SNAI1 的表达。KDM6B 催化 SNAI1 启动子中组蛋白 H3 Lys 27 三甲基化（H3K27me3）的去甲基化，这对于 SNAI1 的上调很重要。总之，这些发现为 KDM6B 促进神经胶质瘤转移的机制提供了新的见解。
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