JARID2 is involved in transforming growth factor-beta-induced epithelial-mesenchymal transition of lung and colon cancer cell lines

• Published in: PloS one Vol. 9; no. 12; p. e115684
• Main Authors: Tange, Shoichiro, Oktyabri, Dulamsuren, Terashima, Minoru, Ishimura, Akihiko, Suzuki, Takeshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.12.2014; Public Library of Science (PLoS)
• Subjects: Biological activity; Biology and Life Sciences; Biotechnology; Bone morphogenetic proteins; Cadherins - genetics; Cadherins - metabolism; Cancer; Cell cycle; Chromatin; Colon; Colon cancer; Colonic Neoplasms - metabolism; Colorectal cancer; Development and progression; DNA methylation; E-cadherin; Enhancer of Zeste Homolog 2 Protein; Enzymes; Epigenetics; Epithelial-Mesenchymal Transition; Gene expression; Gene regulation; Gene silencing; Genes; Genomics; Growth factors; Histone H3; Histones - metabolism; HT29 Cells; Humans; Immunoprecipitation; Lung cancer; Lung diseases; Lung Neoplasms - metabolism; Lysine; Medical research; Medicine and Health Sciences; Mesenchyme; Methylation; MicroRNAs; MicroRNAs - genetics; miRNA; Polycomb group proteins; Polycomb Repressive Complex 2 - genetics; Polycomb Repressive Complex 2 - metabolism; Prostate; Proteins; Regulatory sequences; Ribonucleic acid; RNA; Stem cells; Studies; Transforming Growth Factor beta - pharmacology; Transforming growth factor-b; Transforming growth factors; Tumor cell lines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0115684

Histone methylation plays a crucial role in various biological and pathological processes including cancer development. In this study, we discovered that JARID2, an interacting component of Polycomb repressive complex-2 (PRC2) that catalyzes methylation of lysine 27 of histone H3 (H3K27), was involved in Transforming Growth Factor-beta (TGF-ß)-induced epithelial-mesenchymal transition (EMT) of A549 lung cancer cell line and HT29 colon cancer cell line. The expression of JARID2 was increased during TGF-ß-induced EMT of these cell lines and knockdown of JARID2 inhibited TGF-ß-induced morphological conversion of the cells associated with EMT. JARID2 knockdown itself had no effect in the expression of EMT-related genes but antagonized TGF-ß-dependent expression changes of EMT-related genes such as CDH1, ZEB family and microRNA-200 family. Chromatin immunoprecipitation assays showed that JARID2 was implicated in TGF-ß-induced transcriptional repression of CDH1 and microRNA-200 family genes through the regulation of histone H3 methylation and EZH2 occupancies on their regulatory regions. Our study demonstrated a novel role of JARID2 protein, which may control PRC2 recruitment and histone methylation during TGF-ß-induced EMT of lung and colon cancer cell lines.