Downregulation of MUC17 was attributable to MUC17 promoter methylation mediated by DNA methyltransferase 1 (DNMT1) H. pylori-enhanced GC cell proliferation and colony formation associated with MUC17 downregulation.
This study suggests that five genetic variations of interest in DNMT1 and DNMT3A are not associated with the presence of gastric cancer, but that rs13420827 may contribute to the gastric cancer risk for those younger individuals, the risk of which may be influenced by the characteristics of tumor.
Collectively, these results indicated that EZH2 and DNMT1-mediated epigenetic silencing contributed to the progression of gastric cancer and glioblastoma, and therefore represents a novel therapeutic target for malignant tumors.
In both GC cell lines and animal models, demethylation was performed either by treatment with 5-aza-2'-deoxycytidine (5-AZA-CdR) or by siRNA targeting DNMT1.
We investigated the associations between SNPs in the DNMT1 gene and risks of developing H. pylori seropositivity, gastric atrophy and gastric cancer in the Chinese population.
These results show that the genetic and phenotypic consequences of silencing DNMT1 in PC3 cells are markedly different from those in colon and gastric cancers, indicating that DNMT1 preferentially targets certain gene promoters.
To address the possibility of DNMT-targeted cancer therapy, we compared the effects of treatment with small interfering ribonucleic acids (siRNAs) specific for DNMT1 or DNMT3b and treatment with 5-aza-dC on transcription, cell growth, and DNA damage in gastric cancer cells.
These results indicate that (1) in contrast to previous findings using other GC sources, our results show that COX-2 activity may not be a critical molecular event during GC formation, (2) the tumor-promoting effects of H pylori infection and Wnt and NF-kappaB activities may be mediated by COX-2-independent pathways, and (3) promoter hypermethylation is the major cause of COX-2 silencing in Dalian GCs, apparently because of increased expression of DNMTs (especially DNMT1).
The average level of mRNA for DNMT1 and DNMT3b in colorectal and stomach cancers was significantly higher than in corresponding non-cancerous mucosae, whereas the average level of mRNA for DNMT2 was significantly lower in colorectal and stomach cancers than in non-cancerous tissue.