COX-2 Gene Promoter Methylation in Patients Infected with
Cyclooxygenase (COX) plays a critical role in peptic ulcer development. COX-2 contains CpG islands in promoter area, which suggests possible epigenetic mechanisms of gene silencing. We evaluated COX-2 gene promoter methylation levels in the gastric mucosa of patients with various gastric diseases. D...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2013-01-01
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| Series: | Clinical Medicine Insights: Gastroenterology |
| Online Access: | https://doi.org/10.4137/CGast.S11917 |
| _version_ | 1811317455796043776 |
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| author | Yosuke Michikawa Hiroshi Yasuda Yoshiyuki Watanabe Ritsuko Oikawa Yoshichika Ohishi Tadateru Maehata Fumio Itoh |
| author_facet | Yosuke Michikawa Hiroshi Yasuda Yoshiyuki Watanabe Ritsuko Oikawa Yoshichika Ohishi Tadateru Maehata Fumio Itoh |
| author_sort | Yosuke Michikawa |
| collection | DOAJ |
| description | Cyclooxygenase (COX) plays a critical role in peptic ulcer development. COX-2 contains CpG islands in promoter area, which suggests possible epigenetic mechanisms of gene silencing. We evaluated COX-2 gene promoter methylation levels in the gastric mucosa of patients with various gastric diseases. DNA was extracted from endoscopic biopsy materials collected from the gastric mucosa. The methylation levels of the COX-2 gene promoter were measured quantitatively by using pyrosequencing. COX-2 mRNA expression in Kato III and AGS cells was measured using real-time PCR. COX-2 gene promoter methylation levels were significantly higher in Helicobacter pylori (HP)-positive cases than in HP-negative cases (27.5% vs. 8.1%, respectively, P < 0.001). COX-2 gene promoter methylation levels in patients in whom HP was successfully eradicated were significantly lower than those in HP-positive cases (18.7% vs. 27.5%, respectively, P < 0.01). We then investigated the effects of COX-2 gene promoter methylation on its mRNA expression in vitro. COX-2 mRNA expression was not observed in Kato III cells, despite the addition of the protein kinase C stimulator a-phorbol 12,13-dibutyrate (PDBu). COX-2 expression was observed after the addition of the demethylating agent 5-Aza-dC and was enhanced by PDBu. HP infection caused a significant increase in the methylation levels of the COX-2 gene promoter in the gastric mucosa. In addition to transcriptional regulation, COX-2 expression is regulated through epigenetic mechanisms. |
| first_indexed | 2024-04-13T12:08:12Z |
| format | Article |
| id | doaj.art-80a352d516bf4149ba7f90caa78d1a5c |
| institution | Directory Open Access Journal |
| issn | 1179-5522 |
| language | English |
| last_indexed | 2024-04-13T12:08:12Z |
| publishDate | 2013-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Gastroenterology |
| spelling | doaj.art-80a352d516bf4149ba7f90caa78d1a5c2022-12-22T02:47:35ZengSAGE PublishingClinical Medicine Insights: Gastroenterology1179-55222013-01-01610.4137/CGast.S11917COX-2 Gene Promoter Methylation in Patients Infected withYosuke Michikawa0Hiroshi Yasuda1Yoshiyuki Watanabe2Ritsuko Oikawa3Yoshichika Ohishi4Tadateru Maehata5Fumio Itoh6Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.Cyclooxygenase (COX) plays a critical role in peptic ulcer development. COX-2 contains CpG islands in promoter area, which suggests possible epigenetic mechanisms of gene silencing. We evaluated COX-2 gene promoter methylation levels in the gastric mucosa of patients with various gastric diseases. DNA was extracted from endoscopic biopsy materials collected from the gastric mucosa. The methylation levels of the COX-2 gene promoter were measured quantitatively by using pyrosequencing. COX-2 mRNA expression in Kato III and AGS cells was measured using real-time PCR. COX-2 gene promoter methylation levels were significantly higher in Helicobacter pylori (HP)-positive cases than in HP-negative cases (27.5% vs. 8.1%, respectively, P < 0.001). COX-2 gene promoter methylation levels in patients in whom HP was successfully eradicated were significantly lower than those in HP-positive cases (18.7% vs. 27.5%, respectively, P < 0.01). We then investigated the effects of COX-2 gene promoter methylation on its mRNA expression in vitro. COX-2 mRNA expression was not observed in Kato III cells, despite the addition of the protein kinase C stimulator a-phorbol 12,13-dibutyrate (PDBu). COX-2 expression was observed after the addition of the demethylating agent 5-Aza-dC and was enhanced by PDBu. HP infection caused a significant increase in the methylation levels of the COX-2 gene promoter in the gastric mucosa. In addition to transcriptional regulation, COX-2 expression is regulated through epigenetic mechanisms.https://doi.org/10.4137/CGast.S11917 |
| spellingShingle | Yosuke Michikawa Hiroshi Yasuda Yoshiyuki Watanabe Ritsuko Oikawa Yoshichika Ohishi Tadateru Maehata Fumio Itoh COX-2 Gene Promoter Methylation in Patients Infected with Clinical Medicine Insights: Gastroenterology |
| title | COX-2 Gene Promoter Methylation in Patients Infected with |
| title_full | COX-2 Gene Promoter Methylation in Patients Infected with |
| title_fullStr | COX-2 Gene Promoter Methylation in Patients Infected with |
| title_full_unstemmed | COX-2 Gene Promoter Methylation in Patients Infected with |
| title_short | COX-2 Gene Promoter Methylation in Patients Infected with |
| title_sort | cox 2 gene promoter methylation in patients infected with |
| url | https://doi.org/10.4137/CGast.S11917 |
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