ArticleNature communications2018
Incompatibility of the circadian protein BMAL1 and HNF4α in hepatocellular carcinoma.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
81 citing papers in PubMed, 107 citations in OpenAlex.
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Dysregulation of circadian clock gene BMAL1 and cell cycle regulator WEE1 in pediatric AML.Molecular biology reports · 2026Article
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Multi-Omics Landscape of Circadian Clock Dysregulation Across the Chronic Liver Disease Spectrum.International journal of molecular sciences · 2026Review
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Comprehensive analysis and therapeutic implications of prognostic value of circadian rhythm genes in hepatocellular carcinoma.Journal of physiology and biochemistry · 2026Article
- Diurnal Regulation and Gene-Specific Vulnerability of Oxidative Alcohol-Metabolizing Enzymes to Circadian Disruption.International journal of molecular sciences · 2026Article
- Circadian clock and cancer.Military Medical Research · 2026Review
- P2-HNF4α alters linoleic acid metabolism and mitigates soybean oil-induced obesity: role for oxylipins.Journal of lipid research · 2025Article
- Circadian rhythm in gastrointestinal cancer: clinical applications and future perspectives.Annals of medicine · 2025Review
- Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.Cell reports · 2025Article
- Differential Control of Growth and Identity by HNF4α Isoforms in Pancreatic Ductal Adenocarcinoma.Molecular cancer research : MCR · 2025Article
- Genetics-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism.Cell metabolism · 2025Article
- Poor sleep and hepatic steatosis contribute to poorer quality of life in people with human immunodeficiency virus.World journal of gastroenterology · 2025Observational
- Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1.PLoS genetics · 2025Article
- The diverse roles of the circadian clock in cancer.Nature cancer · 2025Review
- Rhythm is essential: Unraveling the relation between the circadian clock and cancer.Critical reviews in oncology/hematology · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Unravelling the link between circadian clock genes and brain tumors: From pathological disruptions to potential therapeutic interventions.Frontiers in pharmacology · 2025Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of liver-specific gene expression with potent tumor suppressor activity, yet many liver tumors express HNF4α. This study reveals that P1-HNF4α, the predominant isoform expressed in the adult liver, inhibits expression of tumor promoting genes in a circadian manner. In contrast, an additional isoform of HNF4α, driven by an alternative promoter (P2-HNF4α), is induced in HNF4α-positive human hepatocellular carcinoma (HCC). P2-HNF4α represses the circadian clock gene ARNTL (BMAL1), which is robustly expressed in healthy hepatocytes, and causes nuclear to cytoplasmic re-localization of P1-HNF4α. We reveal mechanisms underlying the incompatibility of BMAL1 and P2-HNF4α in HCC, and demonstrate that forced expression of BMAL1 in HNF4α-positive HCC prevents the growth of tumors in vivo. These data suggest that manipulation of the circadian clock in HNF4α-positive HCC could be a tractable strategy to inhibit tumor growth and progression in the liver.
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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.