CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas

CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas

Author Wisnieski, Fernanda Autor UNIFESP Google Scholar
Calcagno, Danielle Queiroz Google Scholar
Leal, Mariana Ferreira Autor UNIFESP Google Scholar
Santos, Leonardo Caires Autor UNIFESP Google Scholar
Gigek, Carolina Oliveira Autor UNIFESP Google Scholar
Chen, Elizabeth Suchi Autor UNIFESP Google Scholar
Demachki, Samia Google Scholar
Artigiani, Ricardo Autor UNIFESP Google Scholar
Assumpcao, Paulo Pimentel Autor UNIFESP Google Scholar
Lourenco, Laercio Gomes Autor UNIFESP Google Scholar
Burbano, Rommel Rodriguez Google Scholar
Smith, Marilia Cardoso Autor UNIFESP Google Scholar
Abstract CDKN1A is a tumor suppressor gene involved in gastric carcinogenesis and is a potential target for histone deacetylase inhibitor-based therapies. Upregulation of CDKN1A is generally observed in several cell lines after histone deacetylase inhibitor treatment

however, little is known about the histone acetylation status associated with this gene in clinical samples, including gastric tumor tissue samples. Therefore, our goal was to quantify the H3K9 and H4K16 acetylation levels associated with three CDKN1A regions in 21 matched pairs of gastric adenocarcinoma and corresponding adjacent non-tumor samples by chromatin immunoprecipitation and to correlate these data with the gene expression. Our results demonstrated that the -402, -20, and +182 CDKN1A regions showed a significantly increased acetylation level in at least one of the histones evaluated (p < 0.05, for all comparisons), and these levels were positively correlated in gastric tumors. However, an inverse correlation was detected between both H3K9 and H4K16 acetylation at the -402 CDKN1A region and mRNA levels in gastric tumors (r = -0.51, p = 0.02

r = -0.60, p < 0.01, respectively). Furthermore, increased H4K16 acetylation at the -20 CDKN1A region was associated with gastric tumors of patients without lymph node metastasis (p = 0.04). These results highlight the complexity of these processes in gastric adenocarcinoma and contribute to a better understanding of CDKN1A regulation in carcinogenesis.
Keywords CDKN1A
Histone acetylation
Gene expression regulation
Gastric cancer
xmlui.dri2xhtml.METS-1.0.item-coverage Milan
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)
Date 2017
Published in Clinical And Experimental Medicine. Milan, v. 17, n. 1, p. 121-129, 2017.
ISSN 1591-8890 (Sherpa/Romeo, impact factor)
Publisher Springer-Verlag Italia Srl
Extent 121-129
Access rights Closed access
Type Letter
Web of Science ID WOS:000394153500014

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