title: Regulation of histone acetylation by NDRG2 in glioma cells.
abstract: NDRG2, a member of the N-Myc downstream-regulated gene family, was shown to be a putative tumor suppressor gene in glioblastoma and other cancers. Through a bioinformatic analysis, we found that NDRG2 protein contains an acyl carrier domain. In the current study, we therefore hypothesized that NDRG2 may play an important role in the regulation of histone acetylation. Treatment of U251 and U87 glioma cells with trichostatin A, an inhibitor of histone deacetylase, upregulated the expression of NDRG2 and acetylated forms of histones H3 and H4, reduced tumor cell viability and arrested  the cell cycle at the G1/G0 phase. Overexpression of NDRG2 by transfecting glioma cells with adenovirus containing the NDRG2 gene upregulated the levels of acetylated forms of H3 and H4 whereas inhibition of NDRG2 expression by siRNA-mediated knockdown downregulated the level of histone acetylation. Furthermore, NDRG2 siRNA significantly reduced the level of histone acetylation induced by trichostatin A. Taken together, these data demonstrate that NDRG2 can regulate the level of histone acetylation to control glioma cell growth.
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Qin
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Rui
authors.initials: R
authors.lastname: Miao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xinping
authors.initials: X
authors.lastname: Liu
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000107:Acetylation; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005910:Glioma / Q000473:pathology; D051548:Histone Acetyltransferases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C466228:NDRG2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D051548:Histone Acetyltransferases; C022616:thiazolyl blue