期刊
CELL CYCLE
卷 12, 期 13, 页码 2100-2112出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.25142
关键词
tumor progression; histone methylation; transcription; microRNA; epithelial-mesenchymal transition
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [25460266, 22112010, 24590346] Funding Source: KAKEN
Histone methylation is implicated in various biological and pathological processes including cancer development. In this study, we discovered that ectopic expression of KDM5B, a histone H3 lysine 4 (H3K4) demethylase, promoted epithelial-mesenchymal transition (EMT) of cancer cells. KDM5B increased the expression of transcription factors, ZEB1 and ZEB2, followed by downregulation of E-cadherin and upregulation of mesenchymal marker genes. The expression of the microRNA-200 (miR-200) family, which specifically targets ZEB1 and ZEB2, was reduced in the cells with KDM5B overexpression. We found that KDM5B repressed the expression of the miR-200 family by changing histone H3 methylation status of their regulatory regions. The introduction of miR-200 precursor in the cells inhibited EMT induction by KDM5B, suggesting that miR-200 family was a critical downstream mediator of KDM5B-promoted EMT. Furthermore, knockdown of KDM5B was shown to affect the expression of EMT-related genes, indicating the involvement of endogenous KDM5B. Our study demonstrated a novel role of KDM5B histone lysine demethylase in EMT, which may contribute to malignant progression of cancer.
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