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

Aixia Sui; Yongbing Xu; Junjie Yang; Baogen Pan; Jiang Wu; Tao Guo; Yongqing Shen; Xiaoqiang Guo

doi:10.1016/j.neuint.2019.01.006

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

Neurochem Int. 2019 Mar:124:123-129. doi: 10.1016/j.neuint.2019.01.006. Epub 2019 Jan 8.

Authors

Aixia Sui¹, Yongbing Xu², Junjie Yang³, Baogen Pan⁴, Jiang Wu⁴, Tao Guo⁵, Yongqing Shen⁶, Xiaoqiang Guo⁷

Affiliations

¹ Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China. Electronic address: allen_sui77@sina.com.
² Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China; Graduate School, Hebei Medical University, Shijiazhuang, 050051, Hebei, China.
³ Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China.
⁴ Department of Neurosurgery, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China.
⁵ Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China; Department of Neurosurgery, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China.
⁶ Department of Nursing, Hebei University of Chinese Medicine, Shijiazhuang, 050020, Hebei, China.
⁷ The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, Guangdong, China. Electronic address: xiaoqiangguo123@163.com.

PMID: 30633952
DOI: 10.1016/j.neuint.2019.01.006

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.

Keywords: Glioma; Histone demethylase; Invasion; KDM6B; Migration; SNAI1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement / physiology*
Clustered Regularly Interspaced Short Palindromic Repeats / physiology
Gene Expression Regulation, Neoplastic*
Glioma / genetics
Glioma / metabolism*
Glioma / pathology
Humans
Jumonji Domain-Containing Histone Demethylases / biosynthesis*
Jumonji Domain-Containing Histone Demethylases / genetics
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Snail Family Transcription Factors / biosynthesis*
Snail Family Transcription Factors / genetics

Substances

SNAI1 protein, human
Snail Family Transcription Factors
Jumonji Domain-Containing Histone Demethylases
KDM6B protein, human