ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
HDAC6/HNF4α loop mediated by miR-1 promotes bile acids-induced gastric intestinal metaplasia.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Therapeutic effect of metformin on reversing gastric intestinal metaplasia.Chinese medical journal · 2026Trial
- Serum Bile Acid Metabolomics-Based Machine Learning Model for Non-Invasive Diagnosis of Gastric Cancer.Cancer medicine · 2026Article
- A TRIM15-CDX2 loop drives bile acid-induced gastric intestinal metaplasia.Molecular medicine (Cambridge, Mass.) · 2026Article
- Taurolithocholic acid alleviates hepatic glycolipid dysregulation in low-birth-weight piglets by activating HNF4α and FXR.Journal of animal science and biotechnology · 2026Article
- The role of microRNAs in gastritis, intestinal metaplasia, and gastric cancer: a narrative review.Translational cancer research · 2025Review
- Long non-coding RNA PVT1 mediates bile acid-induced gastric intestinal metaplasia via a miR-34b-5p/HNF4α positive feedback loop.Chinese medical journal · 2025Article
- Crosstalk between bile acids and gut microbiota: a potential target for precancerous lesions of gastric cancer.Frontiers in pharmacology · 2025Review
- Advances in modeling gastric intestinal metaplasia: a comprehensive review of experimental models and mechanistic insights.Frontiers in oncology · 2025Review
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- Construct dysregulated miRNA-mRNA interaction networks to conjecture possible pathogenesis for Stomach adenocarcinomas.Cancer biomarkers : section A of Disease markers · 2024Article
- 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
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
- High-fat diet induced cyclophilin B enhances STAT3/lncRNA-PVT1 feedforward loop and promotes growth and metastasis in colorectal cancer.Cell death & disease · 2022Article
- Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review.Cell death discovery · 2022Review
- MicroRNA-1: Diverse role of a small player in multiple cancers.Seminars in cell & developmental biology · 2022Review
- Epigenetic histone acetylation modulating prenatal Poly I:C induced neuroinflammation in the prefrontal cortex of rats: a study in a maternal immune activation model.Frontiers in cellular neuroscience · 2022Article
- HDAC6/FOXP3/HNF4α axis promotes bile acids induced gastric intestinal metaplasia.American journal of cancer research · 2022Article
- Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer.Genes & development · 2022Article
- Bile acids increase intestinal marker expression via the FXR/SNAI2/miR-1 axis in the stomach.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Role of HDAC6 and Its Selective Inhibitors in Gastrointestinal Cancer.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGastric intestinal metaplasia (IM) is considered a precancerous lesion, and bile acids (BA) play a critical role in the induction of IM. Ectopic expression of HNF4α was observed in a BA-induced IM cell model. However, the mechanisms underlying the upregulation of the protein in IM cells remains to be elucidated.
methodsThe effects of HNF4α on gastric mucosal cells in vivo were identified by a transgenic mouse model and RNA-seq was used to screen downstream targets of deoxycholic acid (DCA). The expression of pivotal molecules and miR-1 was detected by immunohistochemistry and in situ hybridization in normal, gastritis and IM tissue slides or microarrays. The transcriptional regulation of HDAC6 was investigated by chromatin immunoprecipitation (ChIP) and luciferase reporter assays.
resultsThe transgenic mouse model validated that HNF4α stimulated the HDAC6 expression and mucin secretion in gastric mucosa. Increased HDAC6 and HNF4α expression was also detected in the gastric IM cell model and patient specimens. HNF4α could bind to and activate HDAC6 promoter. In turn, HDAC6 enhanced the HNF4α protein level in GES-1 cells. Furthermore, miR-1 suppressed the expression of downstream intestinal markers by targeting HDAC6 and HNF4α.
conclusionsOur findings show that the HDAC6/HNF4α loop regulated by miR-1 plays a critical role in gastric IM. Blocking the activation of this loop could be a potential approach to preventing BA-induced gastric IM or even gastric cancer (GC).
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