| RRC ID |
52296
|
| 著者 |
Terashima M, Ishimura A, Wanna-Udom S, Suzuki T.
|
| タイトル |
Epigenetic regulation of epithelial-mesenchymal transition by KDM6A histone demethylase in lung cancer cells.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Histone methylation is associated with various biological and pathological processes including cancer development. KDM6A is a candidate tumor suppressor gene that encodes a histone H3 lysine 27 (H3K27) demethylase. In this study, we discovered that ectopic expression of KDM6A antagonized TGF-β-induced epithelial-mesenchymal transition (EMT) and cell migration of lung cancer cell lines through its demethylase activity. KDM6A counteracted TGF-β-dependent changes in the expression of EMT-related genes such as CDH1/E-cadherin, FN1/Fibronectin, ZEB family and microRNA-200 family. Mechanistic investigations revealed that KDM6A inhibited the recruitment of EZH2 histone H3K27 methyltransferase and H3K27 methylation on the regulatory regions of the target genes such as CDH1 and microRNA-200 family. Knockdown of KDM6A did not proceed EMT by itself, but influenced the expression of specific target genes critical for EMT, suggesting that endogenous KDM6A was involved in EMT-inducing transcriptional program. This study demonstrated a novel regulatory role of KDM6A histone demethylase in the epigenetic control of EMT process in lung cancer cells.
|
| 巻・号 |
490(4)
|
| ページ |
1407-1413
|
| 公開日 |
2017-9-2
|
| DOI |
10.1016/j.bbrc.2017.07.048
|
| PII |
S0006-291X(17)31390-6
|
| PMID |
28698146
|
| MeSH |
A549 Cells
Animals
Antigens, CD
Cadherins / genetics
Cadherins / metabolism
Cell Line, Tumor
Cell Movement
Enhancer of Zeste Homolog 2 Protein / genetics
Enhancer of Zeste Homolog 2 Protein / metabolism
Epigenesis, Genetic*
Epithelial-Mesenchymal Transition*
Fibronectins / genetics
Fibronectins / metabolism
Gene Expression Regulation, Neoplastic*
Genetic Vectors / chemistry
Genetic Vectors / metabolism
Histone Demethylases / genetics*
Histone Demethylases / metabolism
Humans
Lentivirus / genetics
Lentivirus / metabolism
Mice
MicroRNAs / genetics
MicroRNAs / metabolism
Transforming Growth Factor beta / genetics*
Transforming Growth Factor beta / metabolism
Zinc Finger E-box-Binding Homeobox 1 / genetics
Zinc Finger E-box-Binding Homeobox 1 / metabolism
|
| IF |
2.985
|
| 引用数 |
10
|
| リソース情報 |
| ヒト・動物細胞 |
LC-2/ad(RCB0440) |
