ArticleThe Journal of biological chemistry2010
MicroRNAs regulate human hepatocyte nuclear factor 4alpha, modulating the expression of metabolic enzymes and cell cycle.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 148 citations in OpenAlex.
- A bioengineered platform reveals progressive impairment of skeletal muscles by metabolic dysfunction-associated steatotic liver disease-derived factors.Disease models & mechanisms · 2026Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- miR-34-5p mediates 20E-induced autophagy in the fat body of Bombyx mori by targeting Atg1.BMC genomics · 2025Article
- Pharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Review
- Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges.Military Medical Research · 2023Review
- Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis.Cancer discovery · 2023Article
- Recent Advances in Novel Recombinant RNAs for Studying Post-transcriptional Gene Regulation in Drug Metabolism and Disposition.Current drug metabolism · 2023Review
- Liver Damage and microRNAs: An Update.Current issues in molecular biology · 2022Review
- Transcription Factors and ncRNAs Associated withBiomedicines · 2022Article
- hsa-miR-34a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury Via Targeting HNF4α.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- miR-125a-5p attenuates macrophage-mediated vascular dysfunction by targeting Ninjurin1.Cell death and differentiation · 2022Article
- Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity.Frontiers in pharmacology · 2022Review
- Epigenetics and microRNAs in UGT1As.Human genomics · 2021Review
- Controversial roles of hepatocyte nuclear receptor 4 α on tumorigenesis.Oncology letters · 2021Review
- From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis.International journal of molecular sciences · 2021Review
- MicroRNA as an Important Target for Anticancer Drug Development.Frontiers in pharmacology · 2021Review
- Research Trends in the Efficacy of Stem Cell Therapy for Hepatic Diseases Based on MicroRNA Profiling.International journal of molecular sciences · 2020Review
- A feedback circuit of miR-34a/MDM4/p53 regulates apoptosis in chronic lymphocytic leukemia cells.Translational cancer research · 2020Article
- Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte nuclear factor (HNF) 4alpha is a key transcription factor regulating endo/xenobiotic-metabolizing enzymes and transporters. We investigated whether microRNAs are involved in the regulation of human HNF4alpha. Potential recognition elements for miR-24 (MRE24) were identified in the coding region and the 3'-untranslated region (3'-UTR), and those for miR-34a (MRE34a) were identified in the 3'-UTR in HNF4alpha mRNA. The HNF4alpha protein level in HepG2 cells was markedly decreased by the overexpression of miR-24 and miR-34a. The HNF4alpha mRNA level was significantly decreased by the overexpression of miR-24 but not by miR-34a. In luciferase analyses in HEK293 cells, the reporter activity of plasmid containing the 3'-UTR of HNF4alpha was significantly decreased by miR-34a. The reporter activity of plasmid containing the HNF4alpha coding region downstream of the luciferase gene was significantly decreased by miR-24. These results suggest that the MRE24 in the coding region and MRE34a in the 3'-UTR are functional in the negative regulation by mRNA degradation and translational repression, respectively. The down-regulation of HNF4alpha by these microRNAs resulted in the decrease of various target genes such as cytochrome P450 7A1 and 8B1 as well as morphological changes and the decrease of the S phase population in HepG2 cells. We also clarified that the expressions of miR-24 and miR-34a were regulated by protein kinase C/mitogen-activated protein kinase and reactive oxygen species pathways, respectively. In conclusion, we found that human HNF4alpha was down-regulated by miR-24 and miR-34a, the expression of which are regulated by cellular stress, affecting the metabolism and cellular biology.
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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.