ArticleAmerican journal of cancer research2022
HDAC6/FOXP3/HNF4α axis promotes bile acids induced gastric intestinal metaplasia.
Article in American journal of cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 5 citations in OpenAlex.
- The gut microbiome-bile acid-FXR interplay: a pivotal axis in metabolic and gastrointestinal diseases.Gut microbes · 2026Review
- Gastric intestinal metaplasia: unraveling the multifactorial pathogenesis and advancing risk stratification for gastric cancer prevention.Cellular and molecular life sciences : CMLS · 2026Review
- Crosstalk between bile acids and gut microbiota: a potential target for precancerous lesions of gastric cancer.Frontiers in pharmacology · 2025Review
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
- Advances in modeling gastric intestinal metaplasia: a comprehensive review of experimental models and mechanistic insights.Frontiers in oncology · 2025Review
- 5-hydroxymethylcytosine signature in plasma extracellular vesicle DNA as a diagnostic molecular biomarker for precancerous lesions of gastric cancer.Extracellular vesicles and circulating nucleic acids · 2025Article
- Article
- Exploration of gastric carcinogenesis from the relationship between bile acids and intestinal metaplasia and intragastric microorganisms (H. pylori and non-H. pylori).Journal of cancer research and clinical oncology · 2023Review
- Alteration of gastric microbiota and transcriptome in a rat with gastric intestinal metaplasia induced by deoxycholic acid.Frontiers in microbiology · 2023Article
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bile reflux is one of the main causes of gastric intestinal metaplasia (IM) which is an important precancerous lesion. Our previous study has shown that ectopic expression of Histone deacetylase 6 (HDAC6) promotes the activation of intestinal markers in bile acids (BA) induced gastric IM cells; however, the mechanism underlying how HDAC6-mediated epigenetic modifications regulate intestinal markers is not clear. In this study, we aimed to investigate the downstream targets of HDAC6 and the underlying mechanism in the process of BA induced gastric IM. We demonstrated that deoxycholic acid (DCA) upregulated HDAC6 in gastric cells, which further inhibited the transcription of Forkhead box protein 3 (FOXP3). Then, FOXP3 transcriptionally inhibited Hepatocyte nuclear factor 4α (HNF4α), which further inhibits the expression of downstream intestinal markers. These molecules have been shown to be clinically relevant, as FOXP3 levels were negatively correlated with HDAC6 and HNF4α in IM tissues. Transgenic mice experiments confirmed that HNF4α overexpression combined with DCA treatment induced gastric mucosa to secrete intestinal mucus and caused an abnormal mucosal structure. Our findings suggest that HDAC6 reduces FOXP3 through epigenetic modification, thus forming a closed loop HDAC6/FOXP3/HNF4α to promote gastric IM. Inhibition of HDAC6 may be a potential approach to prevent gastric IM in patients with bile reflux.
Indexed as
Identifiers
35411233PMC8984877W4225906935What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.