ArticleSignal transduction and targeted therapy2020
m6A RNA methylation-mediated HNF3γ reduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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85 citing papers in PubMed, 117 citations in OpenAlex.
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- IGF2BP2 Drives Thyroid Cancer Dedifferentiation Through m6A-Dependent STAT1 mRNA Destabilization.International journal of biological sciences · 2026Article
- Therapy-induced mRNA, rRNA and tRNA methylation alterations confer tolerance phenotype in tumor cells: mechanism and implications.International journal of biological sciences · 2026Review
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Decoding the role of mNeurochemistry international · 2025Review
- RNA methylation in hepatocellular carcinoma: from metabolic reprogramming and immune escape mechanisms to small molecule inhibitor development.Journal of translational medicine · 2025Review
- Comprehensive profiling of RNA modification-related genes identifies RNA mExperimental & molecular medicine · 2025Article
- Epigenetic Alterations in Hepatocellular Carcinoma: Mechanisms, Biomarkers, and Therapeutic Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting m6A methylation for early diagnosis and precision medicine in hepatocellular carcinoma.Cancer cell international · 2025Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Decitabine regulates the resistance of HCC to sorafenib through demethylation.Clinical epigenetics · 2025Article
- Role, mechanism, and application of N6-methyladenosine in hepatobiliary carcinoma.World journal of gastrointestinal oncology · 2025Review
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- Exploration of the mechanism of 5-Methylcytosine promoting the progression of hepatocellular carcinoma.Translational oncology · 2025Article
- The inspiration of methyltransferase in RNA methylation modification for targeted therapy of malignant tumors.Frontiers in immunology · 2025Review
- Circ_0060927 regulates miR-331-3p/ERK/MAPK pathway reaction in non-small cell lung cancer through METTL14-driven methylation.Frontiers in oncology · 2025Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte nuclear factor 3γ (HNF3γ) is a hepatocyte nuclear factor, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unclear. Herein, we report that HNF3γ expression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival. Moreover, our data suggested that the HNF3γ reduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γ mRNA. HNF3γ expression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells. Interestingly, HNF3γ delivery promoted differentiation of not only HCC cells but also liver CSCs, which led to suppression of HCC growth. Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules, which could synergistically facilitate HCC cell differentiation. More importantly, enforced HNF3γ expression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression, which are major membrane transporters for sorafenib uptake. Clinical investigation showed that patient-derived HCC xenografts with high HNF3γ expression exhibited a sorafenib response and patients with high HCC HNF3γ levels benefited from sorafenib therapy. Together, these results suggest that HNF3γ plays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients.
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