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Histone demethylase KDM6B regulates 1,25‐dihydroxyvitamin D3‐induced senescence in glioma cells
Author(s) -
Sui Aixia,
Xu Yongbing,
Pan Baogen,
Guo Tao,
Wu Jiang,
Shen Yongqing,
Yang Junjie,
Guo Xiaoqiang
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28431
Subject(s) - demethylase , gene knockdown , senescence , cancer research , histone , glioma , biology , downregulation and upregulation , histone methylation , histone h3 , epigenetics , microbiology and biotechnology , chemistry , cell culture , gene expression , dna methylation , biochemistry , genetics , gene
Vitamin D is a fat‐soluble vitamin and plays an important role in calcium absorption and bone development, whose lack can cause a variety of diseases, including cancer. Human epidemiological studies suggested that vitamin D3 deficiency might increase glioma incidence, but molecular mechanism is less understood. In this study, we show that 1,25‐dihydroxyvitamin D3 (the active form of vitamin D3) induces senescence of glioma cells and increases the expression of senescence markers, INK4A and cyclin‐dependent kinase inhibitor 1A (CDKN1A). 1,25‐Dihydroxyvitamin D3 also upregulates the expression of histone demethylase, KDM6B. Knockdown of KDM6B attenuates 1,25‐dihydroxyvitamin D3‐induced senescence and upregulation of INK4A and CDKN1A. KDM6B promotes the transcription of INK4A by eliminating the trimethylation of repressive marker H3K27me3 near its promoter. This study reveals a new regulatory mechanism involved in vitamin D3 inhibition on gliomas, which is beneficial to prevention and adjuvant therapy of glioma.