ArticleBritish journal of pharmacology2019
Epigenetic events involved in organic cation transporter 1-dependent impaired response of hepatocellular carcinoma to sorafenib.
Article in British journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Pharmacological strategies to enhance the response of hepatoblastoma to chemotherapy through MDR1 inhibition.Acta pharmacologica Sinica · 2026Article
- 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
- Investigating the diagnostic and prognostic significance of genes related to fatty acid metabolism in hepatocellular carcinoma.BMC gastroenterology · 2024Article
- The critical role of circular RNAs in drug resistance in gastrointestinal cancers.Medical oncology (Northwood, London, England) · 2023Review
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
- Insights into the role of nucleotide methylation in metabolic-associated fatty liver disease.Frontiers in immunology · 2023Review
- MJDs family members: Potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma.Frontiers in genetics · 2022Article
- A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients.International journal of molecular sciences · 2021Article
- Drug-Drug Interactions at Organic Cation Transporter 1.Frontiers in pharmacology · 2021Review
- How Dysregulated Ion Channels and Transporters Take a Hand in Esophageal, Liver, and Colorectal Cancer.Reviews of physiology, biochemistry and pharmacology · 2021Review
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- Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity.Cancers · 2020Review
- Role ofExpert opinion on drug metabolism & toxicology · 2020Review
- Role of Genetic Variations in the Hepatic Handling of Drugs.International journal of molecular sciences · 2020 · on this mapReview
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- Sorafenib Activity and Disposition in Liver Cancer Does Not Depend on Organic Cation Transporter 1.Clinical pharmacology and therapeutics · 2020Article
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Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe expression of the human organic cation transporter-1 (hOCT1, gene SLC22A1) is reduced in hepatocellular carcinoma (HCC). The molecular bases of this reduction and its relationship with the poor response of HCC to sorafenib were investigated. EXPERIMENTAL APPROACH: HCC transcriptomes from 366 samples available at TCGA were analysed. Alternative splicing was determined by RT-PCR. The role of miRNAs in SLC22A1 downregulation was investigated. Expression of Oct1 was measured in rodent HCC models (spontaneously generated in Fxr KEY
resultshOCT1 overexpression enhanced sorafenib, but not regorafenib, quinine-inhibitable uptake by hepatoma cells. In rodent HCC, Oct1 was downregulated, which was accompanied by impaired sorafenib uptake. In mice with s.c.-implanted HCC, sorafenib inhibited the growth of hOCT1 overexpressing tumours. In human HCC, hOCT1 expression was inversely correlated with SLC22A1 promoter methylation, whereas demethylation with decitabine enhanced hOCT1 expression in hepatoma cells. Increased proportion of aberrant hOCT1 mRNA variants was found in HCC samples. In silico analysis identified six miRNAs as candidates to target hOCT1 mRNA. When overexpressed in HepG2 cells a significant hOCT1 mRNA decay was induced by hsa-miR-330 and hsa-miR-1468. Analysis of 39 paired tumour/adjacent samples from TCGA revealed that hsa-mir-330 was consistently upregulated in HCC. CONCLUSION AND IMPLICATIONS: Impaired hOCT1 expression/function in HCC, in part due to epigenetic modifications, plays an important role in the poor pharmacological response of this cancer to sorafenib.
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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.