title: JARID2 is involved in transforming growth factor-beta-induced epithelial-mesenchymal transition of lung and colon cancer cell lines.
abstract: 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.
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tange
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Dulamsuren
authors.initials: D
authors.lastname: Oktyabri
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishimura
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D058750:Epithelial-Mesenchymal Transition; D019073:HT29 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D006657:Histones; C547777:JARID2 protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2