ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2020
Loss of HNF1α Function Contributes to Hepatocyte Proliferation and Abnormal Cholesterol Metabolism via Downregulating miR-122: A Novel Mechanism of MODY3.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- MicroRNAs as the promising markers of comorbidities in childhood obesity-A systematic review.Pediatric obesity · 2022Pooled it
- Engineered miR-122 inhibitors preserve endothelial mitochondrial function and prevent vascular dysfunction in obesity-associated prediabetes.Molecular therapy. Nucleic acids · 2026Article
- Review
- Hepatocyte nuclear factor 1 in renal lipid metabolism: molecular mechanisms and therapeutic potentials.Cell biology and toxicology · 2025Review
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone ofJournal of Zhejiang University. Science. B · 2023Article
- Dominant-negative HNF1α mutant promotes liver steatosis and inflammation by regulating hepatic complement factor D.iScience · 2023Article
- Transcriptional control by HNF-1: Emerging evidence showing its role in lipid metabolism and lipid metabolism disorders.Genes & diseases · 2022Review
- Association of HNF1A gene variants and haplotypes with metabolic syndrome: a case-control study in the Tunisian population and a meta-analysis.Diabetology & metabolic syndrome · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeMutations in hepatocyte nuclear factor 1α (HNF1α) are the cause of maturity-onset diabetes of the young type 3 (MODY3) and involved in the development of hepatocellular adenoma and abnormal lipid metabolism. Previously, we have found that the serum microRNA (miR)-122 levels in MODY3 patients were lower than those in type 2 diabetes mellitus and healthy controls. This study aimed to investigate the mechanism of decreased miR-122 levels in patients with MODY3 and whether low levels of miR-122 mediate tumorigenesis and abnormal lipid metabolism associated with HNF1α deficiency in human hepatocytes.
methodsThe expression of miR-122 was examined by real-time PCR. Dual-luciferase reporter assay was performed to confirm the transcriptional regulation of miR-122 by HNF1α. HepG2 cells were transfected with siRNA or miRNA mimic to downregulate or upregulate the expression of HNF1α or miR-122, respectively. CCK-8 and colony formation assay were used to determine cell proliferation. Lipid accumulation was examined by Oil Red O staining and intracellular triglyceride and cholesterol quantification assays.
resultsHNF1α regulated the expression of miR-122 by directly binding to its promoter. Knockdown of HNF1α in HepG2 cells reduced the expression of miR-122, increased proliferation and promoted intracellular cholesterol accumulation. Overexpression of miR-122 partially rescued the phenotypes associated with HNF1α deficiency in human hepatocytes. Mechanistically, HNF1α modulated cholesterol homeostasis via miR-122-dependent activation of sterol regulatory element-binding protein-2 (SREBP-2) and regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9). Moreover, circulating miR-122 levels were associated with serum cholesterol levels.
conclusionLoss of HNF1α function led to hepatocyte proliferation and abnormal cholesterol metabolism by downregulating miR-122. Our findings revealed a novel mechanism that low levels of miR-122 mediate tumorigenesis and abnormal lipid metabolism associated with MODY3. MiR-122 may be a potential therapeutic target for the treatment of MODY3.
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