ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Bile acids promote diethylnitrosamine-induced hepatocellular carcinoma via increased inflammatory signaling.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Bile acids as a "new hormone" in aging-related liver disease.Life medicine · 2026Review
- Integrated serum proteomics and metabolomics reveal an INR-associated multi-omics signature in hepatocellular carcinoma.Clinical proteomics · 2026Article
- Influence of Gut Microbiota on Response to Immune Check Point Inhibitors in MASLD Patients With HCC: Unraveling the Connection.Cancer medicine · 2026Review
- Captivating Synergistic, Dose-Dependent Anticancer Effects of Tumor-Regulation Modulators Chloroquine and Ivermectin Completely Abolished by an Opposing Modulator, Deoxycholic Acid, in Hamster Fibrosarcoma: In Vivo, In Vitro, and Literature Review.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Zhuyu pill relieves cholestasis in rats by modulating the expression of lncRNAs and circRNAs.Frontiers in pharmacology · 2026Article
- Regulation of bile acids homeostasis: a feasible and versatile way to treat or diagnose liver disorders.Frontiers in nutrition · 2026Review
- Article
- The Roles and Clinical Significance of Major Hepatic-Derived Metabolites in Hepatocellular Carcinoma.Journal of gastroenterology and hepatology · 2025Review
- Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomization (MR).Ecancermedicalscience · 2024Article
- Taurohyocholic acid acts as a potential predictor of the efficacy of tyrosine kinase inhibitors combined with programmed cell death-1 inhibitors in hepatocellular carcinoma.Frontiers in pharmacology · 2024Article
- Impact of elobixibat on liver tumors, microbiome, and bile acid levels in a mouse model of nonalcoholic steatohepatitis.Hepatology international · 2023Article
- Tumor-mediated microbiota alteration impairs synaptic tagging/capture in the hippocampal CA1 area via IL-1β production.Communications biology · 2023Article
- Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Dysregulation and oncogenic activities of ubiquitin specific peptidase 2a in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2023Article
- Hepatocellular carcinoma: Novel understandings and therapeutic strategies based on bile acids (Review).International journal of oncology · 2022Review
- Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis.Journal of clinical medicine · 2022Article
- Development of a Bile Acid-Related Gene Signature for Predicting Survival in Patients with Hepatocellular Carcinoma.Computational and mathematical methods in medicine · 2022Article
- Dietary and Genetic Cholesterol Loading Rather Than Steatosis Promotes Liver Tumorigenesis and NASH-Driven HCC.Cancers · 2021Article
- MITOCHONDRIAL CHOLESTEROL AND CANCER.Seminars in cancer biology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and the third leading cause of cancer related deaths. Previous studies have implicated bile acids in pathogenesis of HCC, but the mechanisms are not known. We investigated the mechanisms of HCC tumor promotion by bile acids the diethylnitrosamine (DEN)-initiation-cholic acid (CA)-induced tumor promotion protocol in mice. The data show that 0.2% CA treatment resulted in threefold increase in number and size of DEN-induced liver tumors. All tumors observed in DEN-treated mice were well-differentiated HCCs. The HCCs observed in DEN-treated CA-fed mice exhibited extensive CD3-, CD20-, and CD45-positive inflammatory cell aggregates. Microarray-based global gene expression studies combined with Ingenuity Pathway Analysis revealed significant activation of NF-κB and Nanog in the DEN-treated 0.2% CA-fed livers. Further studies showed significantly higher TNF-α and IL-1β mRNA, a marked increase in total and phosphorylated-p65 and phosphorylated IκBα (degradation form) in livers of DEN-treated 0.2% CA-fed mice. Treatment of primary mouse hepatocytes with various bile acids showed significant induction of stemness genes including Nanog, KLF4, Sox2, and Oct4. Quantification of total and 20 specific bile acids in liver, and serum revealed a tumor-associated bile acid signature. Finally, quantification of total serum bile acids in normal, cirrhotic, and HCC human samples revealed increased bile acids in serum of cirrhotic and HCC patients. Taken together, these data indicate that bile acids are mechanistically involved pathogenesis of HCC and may promote HCC formation via activation of inflammatory signaling.
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