ArticleCellular oncology (Dordrecht, Netherlands)2025
Regulatory factor X1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by transcriptional regulation of BECN1.
Article in Cellular oncology (Dordrecht, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global research status and frontiers on ferroptosis in hepatocellular carcinoma: a comprehensive bibliometric and visualized analysis.Frontiers in immunology · 2025Pooled it
- Pharmacological targeting of ferroptosis in cancer: mechanisms, tumor immunity, and translational challenges.Pharmacological reports : PR · 2026Review
- USP10 confers lenvatinib resistance in hepatocellular carcinoma by deubiquitinating the GPX2.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Histone lactylation-mediated glycolysis-ferroptosis axis in neurological diseases.Frontiers in molecular neuroscience · 2026Review
- Research progress on ferroptosis and PARP inhibitors in ovarian cancer: action mechanisms and resistance mechanisms.Frontiers in pharmacology · 2025Review
- RFX1 Regulates Immune Microenvironment and Predicts Immunotherapy Response in Colon Cancer: A Multi-Omics and Clinical Analysis.Oncology research · 2025Article
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Authors and funding
18 authors.
Funding
Abstract
backgroundSorafenib is a commonly used first-line kinase-targeted drug for advanced hepatocellular carcinoma (HCC) patients suffering from limited efficacy. Emerging evidence indicates that sorafenib exerts anti-cancer activity through the induction of ferroptosis in HCC cells, but the underlying mechanism is still unclear.
methodsThe whole transcriptome sequencing and bioinformatics analysis were used to screen for target genes. The expression and subcellular localization of regulatory factor X1 (RFX1) were determined through immunohistochemistry, immunofluorescence, PCR and western blot analyses. The impact of RFX1 on HCC cell growth was assessed using CCK8, colony formation assays, cell death assays, and animal experiments. Glutathione measurement, iron assay and lipid peroxidation detection assays were performed to investigate ferroptosis of HCC cells. The regulatory mechanism of RFX1 in HCC was investigated by sgRFX1, co-IP, ChIP and luciferase experiments. Immunohistochemical and survival analyses were performed to examine the prognostic significance of RFX1 in HCC.
resultsIn this study, we found that RFX1 promote ferroptosis in HCC cells. Further, we showed that sorafenib induces cell death through RFX1-mediated ferroptosis in HCC cells. The enhancing effect of RFX1 on HCC cell ferroptosis is largely dependent on inhibition of cystine/glutamate antiporter (system Xc-) activity through the BECN-SLC7A11 axis, where RFX1 directly binds to the promoter region of BECN1 and upregulates BECN1 expression. In addition, a STAT3-RFX1-BECN1 signalling loop was found to promote RFX1 expression in HCC cells.
conclusionsOur study reveals a novel mechanism underlying sorafenib-induced HCC cell death.
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