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KMID : 1034820130090030227
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Molecular & Cellular Toxicology
2013 Volume.9 No. 3 p.227 ~ p.233
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GKN1 and miR-185 are associated with CpG island methylator phenotype in gastric cancers
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Choi Byung-Joon
Yoon Jung-Hwan
Choi Won-Suk
Kim Olga
Nam Suk-Woo
Lee Jung-Young
Park Won-Sang
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Abstract
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Epigenetic modifications including aberrant DNA methylation play a significant role in cancer development. We investigated mRNA expression levels of GKN1, miR-185, DNMT1 and EZH2, as well as their association with the CpG island methylator phenotype (CIMP) in gastric cancers. Twenty-four incident gastric carcinomas were characterized for methylation status and mRNA expression levels of GKN1, miR-185, DNMT1 and EZH2 were examined. In gastric cancer, methylation frequencies in the Mint1, Mint2, E-CDH, hMLH1 and p16 genes were 41.7%, 41.7%, 29.2%, 25% and 4.2%, respectively. At least one gene was methylated in 19 (79.2%) cases. When the methylation status was classified as high (H) and low (L), 11 (45.8%) cases showed CIMP-H. Twentytwo (91.7%) of 24 gastric cancers showed decreased expression of GKN1 and miR-185, compared to samples from the corresponding non-cancerous gastric mucosa. Increased expression of DNMT1 and EZH2 was found in 21 (87.5%) gastric cancers. Statistically, there was a close association between the methylation status and expression levels of GKN1, miR-185, DNMT1 and EZH2 (P<0.05). These results suggest that GKN1 and miR-185 may be representative and predictive biomarkers for methylation status in gastric carcinogenesis.
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KEYWORD
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Methylation, GKN1, miR-185, DNMT1, Gastric cancer
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