ArticleCancer cell international2019
Role of hepatocyte nuclear factor 4 alpha in cell proliferation and gemcitabine resistance in pancreatic adenocarcinoma.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Global trends in resistance studies of gemcitabine and pancreatic cancer: a bibliometric and visual analysis from 2010 to 2024.Frontiers in pharmacology · 2025Pooled it
- KLF5 enables dichotomous lineage programs in pancreatic cancer via the AAA+ ATPase coactivators RUVBL1 and RUVBL2.Nature communications · 2025Article
- Cell-permeated peptide P-T3H2 inhibits malignancy on hepatocellular carcinoma through stabilizing HNF4α protein.Discover oncology · 2024Article
- LncRNAs are involved in regulating ageing and age-related disease through the adenosine monophosphate-activated protein kinase signalling pathway.Genes & diseases · 2024Review
- Delineating the role of nuclear receptors in colorectal cancer, a focused review.Discover oncology · 2024Review
- Gut microbiota trigger host liver immune responses that affect drug-metabolising enzymes.Frontiers in immunology · 2024Review
- Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.Neurochemical research · 2023Article
- CES2 sustains HNF4α expression to promote pancreatic adenocarcinoma progression through an epoxide hydrolase-dependent regulatory loop.Molecular metabolism · 2022Article
- Review
- Controversial roles of hepatocyte nuclear receptor 4 α on tumorigenesis.Oncology letters · 2021Review
- LncRNA HOTAIR recruits SNAIL to inhibit the transcription of HNF4α and promote the viability, migration, invasion and EMT of colorectal cancer.Translational oncology · 2021Article
- Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment.Experimental & molecular medicine · 2021Review
- Human equilibrative nucleoside transporter-1 and deoxycytidine kinase can predict gemcitabine effectiveness in Egyptian patients with Hepatocellular carcinoma.Journal of clinical laboratory analysis · 2020Article
- The Clinical Significance of PIWIL3 and PIWIL4 Expression in Pancreatic Cancer.Journal of clinical medicine · 2020Article
- Long non-coding RNA LINC00858 exerts a tumor-promoting role in colon cancer via HNF4α and WNK2 regulation.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Role of Damage DNA-Binding Protein 1 in Pancreatic Cancer Progression and Chemoresistance.Cancers · 2019Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocyte nuclear factor 4α (HNF4α) is a tissue-specific transcription factor that regulates the expression of numerous genes in hepatocytes and pancreatic β cells. HNF4α has been reported to affect cell proliferation and chemoresistance in several cancers. However, the role of HNF4α in pancreatic adenocarcinoma (PDAC) has not been studied extensively and remains unclear.
methodsBy utilizing immunohistochemical (IHC) staining, we measured the expression of HNF4α in PDAC tissues. By silencing HNF4α in PDAC cell lines, we assessed the impact of HNF4α on pancreatic cancer cell proliferation and gemcitabine sensitivity. We used CCK8 and colony formation assays to examine the effect of HNF4α on cell proliferation. A flow cytometry assay was used to assess cell apoptosis. The expression of gemcitabine-related genes was detected by quantitative real‑time PCR (qRT-PCR) and Western blotting. IHC was utilized to assess the correlation between HNF4α and human equilibrative nucleoside transporter 1 (hENT1) expression in PDAC patients. Chromatin immunoprecipitation (ChIP) and dual‑luciferase reporter assays were used to confirm that hENT1 is a target gene of HNF4α.
resultsIncreased HNF4α expression was detected in PDAC tissues; patients with higher HNF4α expression displayed worse prognosis. To elucidate the function of HNF4α, we examined its role in pancreatic cancer cell proliferation, apoptosis and gemcitabine resistance. In HNF4α-silenced Capan-1 and MiaPaCa-2 cells, we observed decreased cell proliferation and increased sensitivity to gemcitabine compared to those of controls. The mechanism of HNF4α in gemcitabine-related chemosensitivity was then explored. In response to HNF4α silencing, the expression levels of gemcitabine-related proteins, hENT1 and deoxycytidine kinase (dCK) were significantly increased. Additionally, hENT1 was negatively correlated with HNF4α in PDAC tissue samples. Moreover, we identified hENT1 as a downstream target of HNF4α.
conclusionHNF4α is a prognostic marker for overall survival, is required for pancreatic cancer cell proliferation and promotes resistance to gemcitabine by downregulating hENT1. Therefore, targeting HNF4α might reverse gemcitabine resistance and provide novel treatment strategies for PDAC.
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