title: PLU1 histone demethylase decreases the expression of KAT5 and enhances the invasive activity of the cells.
abstract: PLU1 is a candidate oncogene that encodes H3K4 (Lys(4) of histone H3) demethylase. In the present study, we found that ectopic expression of PLU1 enhanced the invasive potential of the weakly invasive cells dependent on its demethylase activity. PLU1 was shown to repress the expression of the KAT5 gene through its H3K4 demethylation on the promoter. The regulation of KAT5 by PLU1 was suggested to be responsible for PLU1-induced cell invasion. First, knockdown of KAT5 similarly increased the invasive potential of the cells. Secondly, knockdown of PLU1 in the highly invasive cancer cells increased KAT5 expression and reduced the invasive activity. Thirdly, simultaneous knockdown of KAT5 partially relieved the suppression of cell invasion imposed by PLU1 knockdown. Finally, we found that CD82, which was transcriptionally regulated by KAT5, might be a candidate effector of cell invasion promoted by PLU1. The present study demonstrated a functional contribution of PLU1 overexpression with concomitant epigenetic dysregulation in cancer progression.
authors.affiliation: Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yoshida
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishimura
authors.forename: Minoru
authors.initials: M
authors.lastname: Terashima
authors.forename: Zanabazar
authors.initials: Z
authors.lastname: Enkhbaatar
authors.forename: Naohito
authors.initials: N
authors.lastname: Nozaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Satou
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D051861:Kangai-1 Protein / Q000235:genetics / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: C497688:CD82 protein, human; D004268:DNA-Binding Proteins; D051861:Kangai-1 Protein; D056484:Jumonji Domain-Containing Histone Demethylases; C485614:Kdm5b protein, mouse; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5