Methylation of the CDX2 promoter in H. pylori-infected gastric mucosa increases with age and its rapid demethylation in gastric tumors is associated with upregulated gene expression

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Title
Methylation of the CDX2 promoter in H. pylori-infected gastric mucosa increases with age and its rapid demethylation in gastric tumors is associated with upregulated gene expression
Author(s)
Hee Jin Kim; Eun Hye Seo; Dong Hyuck Bae; Keeok Haam; Hae-Ran Jang; Jong Lyul ParkJeong Hwan KimMirang KimSeon-Young Kim; H Y Jeong; K S Song; Yong Sung Kim
Bibliographic Citation
Carcinogenesis, vol. 41, no. 10, pp. 1341-1352
Publication Year
2020
Abstract
Pathological changes in the epigenetic landscape of chromatin are hallmarks of cancer. The caudal-type homeobox gene CDX2 is not expressed in normal gastric epithelia but rather in adult intestinal epithelia, and it is overexpressed in intestinal metaplasia (IM). However, it remains unclear how CDX2 transcription is suppressed in normal gastric epithelial cells and overexpressed in IM. Here, we demonstrate that methylation of the CDX2 promoter increases with age in Helicobacter pylori-positive, noncancerous gastric tissue, whereas the promoter is demethylated in paired gastric tumors in which CDX2 is upregulated. Moreover, we also found that the CDX2 promoter is demethylated in IM as well as gastric tumor. Immunohistochemistry revealed that CDX2 is present in foci of parts of the gastric mucosae but highly expressed in IM as well as in gastric tumors, suggesting that the elevated level of CDX2 in IM and gastric tumors may be attributable to promoter demethylation. Our data suggest that CDX2 repression may be associated with promoter methylation in noncancerous H. pylori-positive mucosa but its upregulation might be attributable to increased promoter activity mediated by chromatin remodeling during gastric carcinogenesis.
ISSN
0143-3334
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/carcin/bgaa083
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Korea Bioinformation Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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