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Aurora-A promotes lenvatinib resistance experimentally through hsa-circ-0058046/miR-424-5p/FGFR1 axis in hepatocellular carcinoma

  • 0Department of Medical Oncology, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, China.
International Journal of Immunopathology and Pharmacology +

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February 3, 2025

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February 3, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Aurora-A dysregulation drives lenvatinib resistance in hepatocellular carcinoma (HCC) by activating the hsa-circ-0058046/miR-424-5p/FGFR1 pathway. Targeting Aurora-A with MLN-8237 combined with lenvatinib overcomes this resistance.

Area Of Science

  • Oncology
  • Molecular Biology
  • Pharmacology

Background

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide.
  • Lenvatinib is a targeted therapy for HCC, but resistance often develops.
  • The molecular mechanisms underlying lenvatinib resistance in HCC require further elucidation.

Purpose Of The Study

  • To investigate the role of Aurora-A in lenvatinib resistance in hepatocellular carcinoma (HCC).
  • To explore the potential of targeting Aurora-A as a therapeutic strategy for overcoming lenvatinib resistance in HCC.

Main Methods

  • Bioinformatics analysis and drug sensitivity assays were employed to assess the correlation between Aurora-A expression and lenvatinib resistance in HCC cell lines.
  • In vitro and in vivo functional experiments were conducted using lenvatinib and the Aurora-A inhibitor MLN-8237.
  • Molecular mechanisms were investigated using circRNA microarray, RNA immunoprecipitation (RIP), RNA pull-down, and dual-luciferase reporter assays.

Main Results

  • Aurora-A expression was positively correlated with lenvatinib resistance in HCC cells.
  • Combined treatment with lenvatinib and MLN-8237 synergistically inhibited HCC cell proliferation.
  • Aurora-A was found to induce FGFR1 expression via the hsa-circ-0058046/miR-424-5p/FGFR1 axis, promoting lenvatinib resistance.

Conclusions

  • Aurora-A promotes lenvatinib resistance in HCC through the hsa-circ-0058046/miR-424-5p/FGFR1 pathway.
  • Aurora-A represents a potential therapeutic target for overcoming lenvatinib resistance in HCC patients.
  • Combination therapy with lenvatinib and MLN-8237 demonstrates promise for clinical application in treating resistant HCC.

Keywords:

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