BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer

BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer

Author Wisnieski, Fernanda Autor UNIFESP Google Scholar
Leal, Mariana Ferreira Autor UNIFESP Google Scholar
Calcagno, Danielle Queiroz Google Scholar
Santos, Leonardo Caires Autor UNIFESP Google Scholar
Gigek, Carolina Oliveira Autor UNIFESP Google Scholar
Chen, Elizabeth Suchi Autor UNIFESP Google Scholar
Artigiani, Ricardo Autor UNIFESP Google Scholar
Demachki, Samia Google Scholar
Assumpcao, Paulo Pimentel Google Scholar
Lourenco, Laercio Gomes Autor UNIFESP Google Scholar
Burbano, Rommel Rodriguez Google Scholar
Smith, Marilia Cardoso Autor UNIFESP Google Scholar
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. (C) 2016 Wiley Periodicals, Inc.
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Grant number FAPESP: 2009/07145-9
CAPES: 201567/2009-1
Date 2017
Published in Journal Of Cellular Biochemistry. Hoboken, v. 118, n. 4, p. 869-877, 2017.
ISSN 0730-2312 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 869-877
Access rights Closed access
Type Article
Web of Science ID WOS:000397420300022

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