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Clinical and Experimental Medicine

, Volume 17, Issue 1, pp 121–129 | Cite as

CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas

  • Fernanda WisnieskiEmail author
  • Danielle Queiroz Calcagno
  • Mariana Ferreira Leal
  • Leonardo Caires Santos
  • Carolina Oliveira Gigek
  • Elizabeth Suchi Chen
  • Sâmia Demachki
  • Ricardo Artigiani
  • Paulo Pimentel Assumpção
  • Laércio Gomes Lourenço
  • Rommel Rodríguez Burbano
  • Marília Cardoso Smith
Letter to the Editor

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 

Notes

Acknowledgments

This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; to MCS, FW, DQC, and MFL), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; to MCS and RRB), and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; to COG).

Compliance with ethical standards

Conflict of interest

None.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Fernanda Wisnieski
    • 1
    Email author
  • Danielle Queiroz Calcagno
    • 2
  • Mariana Ferreira Leal
    • 1
    • 3
  • Leonardo Caires Santos
    • 1
  • Carolina Oliveira Gigek
    • 1
  • Elizabeth Suchi Chen
    • 1
  • Sâmia Demachki
    • 2
  • Ricardo Artigiani
    • 4
  • Paulo Pimentel Assumpção
    • 2
  • Laércio Gomes Lourenço
    • 5
  • Rommel Rodríguez Burbano
    • 6
  • Marília Cardoso Smith
    • 1
  1. 1.Disciplina de Genética, Departamento de Morfologia e GenéticaUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Núcleo de Pesquisas em Oncologia, Hospital João de Barros BarretoUniversidade Federal do ParáBelémBrazil
  3. 3.Departamento de Ortopedia e TraumatologiaUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Departamento de PatologiaUniversidade Federal de São PauloSão PauloBrazil
  5. 5.Disciplina de Gastroenterologia Cirúrgica, Departamento de CirurgiaUniversidade Federal de São PauloSão PauloBrazil
  6. 6.Laboratório de Citogenética Humana, Instituto de Ciências BiológicasUniversidade Federal do ParáBelémBrazil

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