RRC ID 52296
Author Terashima M, Ishimura A, Wanna-Udom S, Suzuki T.
Title Epigenetic regulation of epithelial-mesenchymal transition by KDM6A histone demethylase in lung cancer cells.
Journal 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.
Volume 490(4)
Pages 1407-1413
Published 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
Times Cited 10
Human and Animal Cells LC-2/ad(RCB0440)