Methylation and expression of cyld gene in gastric cancer patients with h. pylori infection
Elham Ghadami,
1 Novin nikbakhsh,
2 Sadegh fattahi,
3 Mohadese kosari,
4 Vahideh mirnia,
5 Haleh akhavan niaki,
6,*
1. Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
2. Department of Surgery, Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran
3. Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran
4. Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
5. Department of Biology, Islamic Azad University, Babol, Iran
6. Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
Abstract
Introduction
Gastric cancer (gc) is one of the most common causes of cancer-related death in the world. infection with helicobacter pylori (h. pylori) is the most common risk factor known for gastric cancer. although h. pylori induced dna methylation of tumor suppressor genes related to gastric cancer initiation and progression has been reported, however, the exact molecular mechanisms underlying induction of aberrant methylation by infection remain largely unknown. the deubiquitinase cylindromatosis (cyld) is a tumor suppressor gene which negatively regulates various signaling pathways including wnt, shh, notch, jnk, and also affects almost all cellular processes. in this study we evaluated cyld promoter methylation status and its expression in gc patients with h. pylori infection.
Methods
This study was performed on tumoral tissues and their corresponding normal counterparts of thirty h. pylori-infected gc patients. cyld mrna expression was compared to the expression of gapdh as a housekeeping gene in cancerous as well as non-tumoral tissues by taqman real-time pcr. cyld promoter methylation status was studied using bisulfite conversion method followed by sequencing.
Results
In total, 20/30 (66.6%) of cases demonstrated cyld gene promoter methylation. among these, 11 cases showed decreased cyld expression, indicating a significant association between hypermethylation and reduced cyld expression (p< 0.05).
Conclusion
These findings showed that h. pylori could induce cyld gene methylation and affect its expression in gastric cancer, which may be an important oncogenic mechanism for the development of gastric carcinomas. further research is needed to provide a deeper knowledge about the role of h. pylori in gastric cancer.
Keywords
Gastric cancer, cyld
