title: BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer.
abstract: Different from genetic alterations, the reversible nature of epigenetic modifications provides an interesting opportunity for the development of clinically relevant therapeutics in different tumors. In this study, we aimed to screen and validate candidate genes regulated by the epigenetic marker associated with transcriptional activation, histone acetylation, in gastric cancer (GC). We first compared gene expression profile of trichostatin A-treated and control GC cell lines using microarray assay. Among the 55 differentially expressed genes identified in this analysis, we chose the up-regulated genes BMP8B and BAMBI for further analyses, that included mRNA and histone acetylation quantification in paired GC and nontumor tissue samples. BMP8B expression was reduced in GC compared to nontumor samples (P < 0.01). In addition, reduced BMP8B expression was associated with poorly differentiated GC (P = 0.02). No differences or histopathological associations were identified concerning BAMBI expression. Furthermore, acetylated H3K9 and H4K16 levels at BMP8B were increased in GC compared to nontumors (P < 0.05). However, reduced levels of acetylated H3K9 and H4K16 were associated with poorly differentiated GC (P < 0.05). Reduced levels of acetylated H3K9 was also associated with diffuse-type histological GC (P < 0.05). Notably, reduced BMP8B mRNA and acetylated H4K16 levels were positively correlated in poorly differentiated GC (P < 0.05). Our study demonstrated that BMP8B seems to be a tumor suppressor gene regulated by H4K16 acetylation in poorly differentiated GC. Therefore, BMP8B may be a potential target for TSA-based therapies in this GC sample subset. J. Cell. Biochem. 118: 869-877, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023900, São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Wisnieski
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023900, São Paulo, Brazil.|Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, Rua Borges Lagoa, 783, São Paulo 04038032, São Paulo, Brazil.
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.affiliation: Núcleo de Pesquisas em Oncologia, Hospital João de Barros Barreto, Universidade Federal do Pará, Avenida Mundurucus, 4487, Belém 66073000, Pará, Brazil.
authors.forename: Danielle Queiroz
authors.initials: DQ
authors.lastname: Calcagno
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023900, São Paulo, Brazil.
authors.forename: Leonardo Caires
authors.initials: LC
authors.lastname: Santos
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023900, São Paulo, Brazil.|Disciplina de Gastroenterologia Cirúrgica, Departamento de Cirurgia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 715, São Paulo 04024002, São Paulo, Brazil.
authors.forename: Carolina Oliveira
authors.initials: CO
authors.lastname: Gigek
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023900, São Paulo, Brazil.
authors.forename: Elizabeth Suchi
authors.initials: ES
authors.lastname: Chen
authors.affiliation: Departamento de Patologia, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023000, São Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Artigiani
authors.affiliation: Núcleo de Pesquisas em Oncologia, Hospital João de Barros Barreto, Universidade Federal do Pará, Avenida Mundurucus, 4487, Belém 66073000, Pará, Brazil.
authors.forename: Sâmia
authors.initials: S
authors.lastname: Demachki
authors.affiliation: Núcleo de Pesquisas em Oncologia, Hospital João de Barros Barreto, Universidade Federal do Pará, Avenida Mundurucus, 4487, Belém 66073000, Pará, Brazil.
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.affiliation: Disciplina de Gastroenterologia Cirúrgica, Departamento de Cirurgia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 715, São Paulo 04024002, São Paulo, Brazil.
authors.forename: Laércio Gomes
authors.initials: LG
authors.lastname: Lourenço
authors.affiliation: Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Correia, 01, Belém 66075110, Pará, Brazil.
authors.forename: Rommel Rodríguez
authors.initials: RR
authors.lastname: Burbano
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023900, São Paulo, Brazil.
authors.forename: Marília Cardoso
authors.initials: MC
authors.lastname: Smith
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*
chemical_list: C405632:BMP8B protein, human; D019485:Bone Morphogenetic Proteins; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C012589:trichostatin A
keywords: BAMBI; BMP8B; GASTRIC CANCER; GENE EXPRESSION REGULATION; HISTONE ACETYLATION; TRICHOSTATIN A