ArticleInternational journal of immunopathology and pharmacology
Aurora-A promotes lenvatinib resistance experimentally through hsa-circ-0058046/miR-424-5p/FGFR1 axis in hepatocellular carcinoma.
Article in International journal of immunopathology and pharmacology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Androgen receptor drives lenvatinib resistance in hepatocellular carcinoma through transcriptional activation of EIF3I and a downstream ceRNA axis.Oncology letters · 2026Article
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
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6 authors.
Funding
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Abstract
objectiveThis study aimed to investigate whether the dysregulation of Aurora-A is involved in lenvatinib resistance in hepatocellular carcinoma.
methodsBioinformatics tools and drug sensitivity assays were used to investigate the association between Aurora-A expression level and lenvatinib resistance in hepatocellular carcinoma cell lines. Cell function experiments had performed after treatment with lenvatinib and/or a selective Aurora-A inhibitor (MLN-8237). CircRNA microarray, RIP, RNA pull-down, and dual-luciferace reporter assay were performed to identify the downstream molecular mechanism of Aurora-A dysregulation.
resultsAurora-A expression was positively correlated with lenvatinib resistance in hepatocellular carcinoma cells. The Aurora-A selective inhibitor MLN-8237, in combination with lenvatinib, synergistically inhibited hepatocellular carcinoma cell proliferation in vitro and vivo, suggesting the Aurora-A might be a potential therapeutic target for lenvatinib resistance. Mechanistically, Aurora-A induced FGFR1 expression through the hsa-circ-0058046/miR-424-5p/FGFR1 axis. Aurora-A promotes lenvatinib resistance through hsa-circ-0058046/miR-424-5p/FGFR1 axis in hepatocellular carcinoma cells. The simultaneous inhibition of FGFR1 by the Aurora-A inhibitor MLN-8237 and lenvatinib overcame lenvatinib resistance in hepatocellular carcinoma cells.
conclusionCollectively, our findings indicate that Aurora-A promotes lenvatinib resistance through the hsa-circ-0058046/miR-424-5p/FGFR1 axis in hepatocellular carcinoma (HCC) cells. These results suggest that Aurora-A may serve as a therapeutic target for HCC patients exhibiting lenvatinib resistance. Furthermore, the combination of lenvatinib and MLN-8237 shows potential for clinical trials aimed at overcoming lenvatinib resistance.
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