인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
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지원사업
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커뮤니티
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초록·키워드
Helicobacter pylori (Hp.) infection is one of the high-risk factors for gastric carcinogenesis (GC). However, the underlying mechanism remains largely unclear. In this study, we uncover an essential role of Hp. infection in mediating tumor suppressor gene silencing in gastric epithelial cells through promoter DNA hypermethylation. Hepatocyte nuclear factor HNF4A was downregulated in GC and predicted poor survival. The in vitro and in vivo assays together confirmed that HNF4A plays a tumor suppressive role in GC. Single-cell analysis showed that HNF4A was selectively expressed in gastric epithelial cells. Besides, the reduced HNF4A expression in GC was due to promoter DNA hypermethylation. More importantly, we have provided strong evidence that Hp. infection causes HNF4A down-regulation by hypermethylation of its gene promoter. Meanwhile, silencing of HNF4A resulted in loss of epithelial polarity and activation of TGFβ-induced EMT signaling in gastric epithelial cells by transcriptionally regulating the expression of downstream target genes. In addition, the rescue assays indicated that Hp. infection activated EMT signaling of gastric epithelial cells in a HNF4A-dependent manner, thereby driving gastric tumorigenesis and metastasis. In conclusion, HNF4A is a tumor suppressor gene in GC. Hp. infection causes silence of the HNF4A gene by hypermethylation of its promoter, which then disrupts epithelial polarity and induces EMT signaling in gastric epithelial cells, thereby driving gastric tumorigenesis and metastasis.
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오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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