Oncotarget

Research Papers:

Epigenetic alterations of gastrokine 1 gene expression in gastric cancer

Filomena Altieri, Chiara Stella Di Stadio, Antonella Federico, Giuseppina Miselli, Maurizio De Palma, Emilia Rippa and Paolo Arcari _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:16899-16911. https://doi.org/10.18632/oncotarget.14817

Metrics: PDF 943 views  |   HTML 1156 views  |   ?  


Abstract

Filomena Altieri1,*, Chiara Stella Di Stadio1,*, Antonella Federico1,*, Giuseppina Miselli1, Maurizio De Palma2, Emilia Rippa1, Paolo Arcari1,3

1Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy

2Hospital A. Cardarelli, Nasples, Italy

3CEINGE, Advanced Biotechnology Scarl, Naples, Italy

*These authors have contributed equally to this work

Correspondence to:

Paolo Arcari, email: paolo.arcari@unina.it

Emilia Rippa, email: emilia.rippa@unina.it

Keywords: gastrokine 1, gastric cancer, epigenetics, histone methylation, histone acetylation

Received: March 02, 2016    Accepted: November 05, 2016    Published: January 25, 2017

ABSTRACT

The gastrokine 1 (GKN1) protein is important for maintaining the physiological function of the gastric mucosa. GKN1 is down-regulated in gastric tumor tissues and derived cell lines and its over-expression in gastric cancer cells induces apoptosis, suggesting a possible role for the protein as a tumor suppressor. However, the mechanism by which GKN1 is inactivated in gastric cancer remains unknown. Here, we investigated the causes of GKN1 silencing to determine if epigenetic mechanisms such as histonic modification could contribute to its down-regulation. To this end, chromatin immunoprecipitation assays for the trimethylation of histone 3 at lysine 9 (H3K9triMe) and its specific histone-lysine N-methyltransferase (SUV39H1) were performed on biopsies of normal and cancerous human gastric tissues. GKN1 down-regulation in gastric cancer tissues was shown to be associated with high levels of H3K9triMe and with the recruitment of SUV39H1 to the GKN1 promoter, suggesting the presence of an epigenetic transcriptional complex that negatively regulates GKN1 expression in gastric tumors. The inhibition of histone deacetylases with trichostatin A was also shown to increase GKN1 mRNA levels. Collectively, our results indicate that complex epigenetic machinery regulates GKN1 expression at the transcriptional level, and likely at the translational level.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 14817