Epigenetic alterations of gastrokine 1 gene expression in gastric cancer
| Autor: | Paolo Arcari, Maurizio De Palma, Antonella Federico, Filomena Altieri, Giuseppina Miselli, Emilia Rippa, Chiara Stella Di Stadio |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Peptide Hormones Gene Expression Transfection Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Cell Line Tumor Histone methylation Gastric mucosa medicine Humans histone methylation Epigenetics Cancer epigenetics Aged Cell Proliferation epigenetics biology gastric cancer histone acetylation Cancer Middle Aged medicine.disease Molecular biology 030104 developmental biology Histone medicine.anatomical_structure Trichostatin A Oncology 030220 oncology & carcinogenesis biology.protein gastrokine 1 Chromatin immunoprecipitation Research Paper medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.14817 |
| Popis: | // Filomena Altieri 1, * , Chiara Stella Di Stadio 1, * , Antonella Federico 1, * , Giuseppina Miselli 1 , Maurizio De Palma 2 , Emilia Rippa 1 , Paolo Arcari 1, 3 1 Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy 2 Hospital A. Cardarelli, Nasples, Italy 3 CEINGE, 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. |
| Databáze: | OpenAIRE |
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