Aberrant methylation of somatostatin receptor 2 gene is initiated in aged gastric mucosa infected with Helicobacter pylori and consequential gene silencing is associated with establishment of inflammatory microenvironment In vitro study

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Title
Aberrant methylation of somatostatin receptor 2 gene is initiated in aged gastric mucosa infected with Helicobacter pylori and consequential gene silencing is associated with establishment of inflammatory microenvironment In vitro study
Author(s)
Hee Jin Kim; Jong Lyul ParkByoung-Ha Yoon; Keeok Haam; Haejeong Heo; Jong-Hwan KimSeon-Young KimMirang Kim; W H Kim; S I Lee; K S Song; K S Ahn; Yong Sung Kim
Bibliographic Citation
Cancers, vol. 14, no. 24, pp. 6183-6183
Publication Year
2022
Abstract
The loss-of-function variants are thought to be associated with inflammation in the stomach. We here aimed to evaluate the extent and role of methylation at the SSTR2 promoter in inflammation and gastric tumor formation. A whole-genome bisulfite sequencing analysis revealed that the SSTR2 promoter was significantly hypermethylated in gastric tumors, dysplasia, and intestinal metaplasia compared to non-tumor tissues from patients with gastric cancer. Using public data, we confirmed SSTR2 promoter methylation in primary gastric tumors and intestinal metaplasia, and even aged gastric mucosae infected with Helicobacter pylori, suggesting that aberrant methylation is initiated in normal gastric mucosa. The loss-of-function of SSTR2 in SNU638 cell-induced cell proliferation in vitro, while stable transfection of SSTR2 in AGS and MKN74 cells inhibited cell proliferation and tumorigenesis in vitro and in vivo. As revealed by a comparison of target genes differentially expressed in these cells with hallmark molecular signatures, inflammation-related pathways were distinctly induced in SSTR2-KO SNU638 cell. By contrast, inflammation-related pathways were inhibited in AGS and MKN74 cells ectopically expressing SSTR2. Collectively, we propose that SSTR2 silencing upon promoter methylation is initiated in aged gastric mucosae infected with H. pylori and promotes the establishment of an inflammatory microenvironment via the intrinsic pathway. These findings provide novel insights into the initiation of gastric carcinogenesis.
Keyword
SSTR2Gastric cancerWGBSHypermethylationInflammation
ISSN
2072-6694
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/cancers14246183
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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