ArticleMolecular cancer2015
Upregulation of microRNA-122 by farnesoid X receptor suppresses the growth of hepatocellular carcinoma cells.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non-Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers.Clinical pharmacology in drug development · 2020Trial
- Bile acid metabolism and hepatocellular carcinoma: mechanisms of drug resistance and intervention strategies.Precision clinical medicine · 2025Review
- Bile acid accumulation induced by miR-122 deficiency in liver parenchyma promotes cancer cell growth in hepatocellular carcinoma.Molecular therapy. Nucleic acids · 2025Article
- A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers.International journal of molecular sciences · 2024Review
- The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2024Review
- Supplementation of Mangiferin to a High-Starch Diet Alleviates Hepatic Injury and Lipid Accumulation Potentially through Modulating Cholesterol Metabolism in Channel Catfish (Antioxidants (Basel, Switzerland) · 2024Article
- Molecular Targets and Signaling Pathways of microRNA-122 in Hepatocellular Carcinoma.Pharmaceutics · 2022Review
- Contributions of microRNAs to Peripheral Insulin Sensitivity.Endocrinology · 2022Review
- Dysbiosis: The first hit for digestive system cancer.Frontiers in physiology · 2022Review
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2021Review
- Non-coding RNA crosstalk with nuclear receptors in liver disease.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Research advances on epigenetics and cancer metabolism.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
- The Nuclear Farnesoid X Receptor Reduces p53 Ubiquitination and Inhibits Cervical Cancer Cell Proliferation.Frontiers in cell and developmental biology · 2021Article
- Article
- MicroRNA 122 Reflects Liver Injury in Children with Intestinal Failure-Associated Liver Disease Treated with Intravenous Fish Oil.The Journal of nutrition · 2020Observational
- Article
- Dysregulated microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Potential as Biomarkers and Therapeutic Targets.Frontiers in oncology · 2020Review
- Upregulation of microRNA-23b-3p induced by farnesoid X receptor regulates the proliferation and apoptosis of osteosarcoma cells.Journal of orthopaedic surgery and research · 2019Article
- Roles of Thyroid Hormone-Associated microRNAs Affecting Oxidative Stress in Human Hepatocellular Carcinoma.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundmicroRNA-122 (miR-122) is the most abundant and specific miRNA in the liver. It acts as an important tumor suppressor in hepatocellular carcinoma (HCC) through regulating its target genes, but details of its own regulation are largely unknown. Farnesoid X receptor (FXR), a transcription factor with multiple functions, plays an important role in protecting against liver carcinogenesis, but it is unclear whether the anti-HCC effect of FXR is involved in the regulation of miR-122.
methodsThe levels of miR-122 and FXR in HCC tissues and cell lines were examined by quantitative real-time PCR (qRT-PCR). qRT-PCR was also used to detect the expression of miR-122 target genes at mRNA level, while Western blotting was used to analyze that of their protein products. The effect of FXR on the transcriptional activity of miR-122 promoter was evaluated by a luciferase reporter assay. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were performed to identify the FXR binding site within miR-122 promoter region. The cell proliferation was analyzed by a CCK-8 assay. The influence of FXR on tumor growth and miR-122 expression in vivo was monitored using HCC xenografts in nude mice.
resultsThe expression of FXR was positively correlated with that of miR-122 in HCC tissues and cell lines. Activation of FXR in HCC cells upregulated miR-122 expression and in turn downregulated the expression of miR-122 target genes including insulin-like growth factor-1 receptor and cyclin G1. FXR bound directly to the DR2 element (-338 to -325) in miR-122 promoter region, and enhanced the promoter's transcriptional activity. Functional experiments showed that the FXR-mediated upregulation of miR-122 suppressed the proliferation of HCC cells in vitro and the growth of HCC xenografts in vivo.
conclusionsmiR-122 is a novel target gene of FXR, and the upregulation of miR-122 by FXR represses the growth of HCC cells, suggesting that FXR may serve as a key transcriptional regulator for manipulating miR-122 expression, and the FXR/miR-122 pathway may therefore be a novel target for the treatment of HCC.
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