CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas

• Published in: Clinical and experimental medicine Vol. 17; no. 1; pp. 121 - 129
• Main Authors: Wisnieski, Fernanda, Calcagno, Danielle Queiroz, Leal, Mariana Ferreira, Santos, Leonardo Caires, Gigek, Carolina Oliveira, Chen, Elizabeth Suchi, Demachki, Sâmia, Artigiani, Ricardo, Assumpção, Paulo Pimentel, Lourenço, Laércio Gomes, Burbano, Rommel Rodríguez, Smith, Marília Cardoso
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.02.2017; Springer Nature B.V
• Subjects: Acetylation; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adult; Cancer therapies; Chromatin Immunoprecipitation; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Epigenesis, Genetic; Female; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Hematology; Histones - genetics; Histones - metabolism; Humans; Internal Medicine; Letter to the Editor; Lymphatic Metastasis; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Grading; Neoplasm Staging; Oncology; Promoter Regions, Genetic; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tumors; Gastric cancer; Histone acetylation; Gene expression regulation; CDKN1A
• ISSN: 1591-8890; 1591-9528
• DOI: 10.1007/s10238-015-0400-3

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.