ETS1-driven transcriptional activation of USP43 promotes lenvatinib resistance in hepatocellular carcinoma through MYH9 stabilization and AKT/BAD signaling - PubMed
6 hours ago
- #lenvatinib resistance
- #USP43
- #hepatocellular carcinoma
- Lenvatinib is a first-line treatment for advanced hepatocellular carcinoma (HCC) but resistance remains a challenge.
- A lenvatinib-resistant HCC cell line (Huh7/LR) was developed, and RNA-seq identified USP43 as a key resistance factor.
- USP43 is overexpressed in resistant HCC cells and tissues, correlating with poor prognosis.
- USP43 promotes HCC cell proliferation, suppresses apoptosis, and enhances lenvatinib resistance.
- ETS1 transcriptionally upregulates USP43, which stabilizes MYH9 by removing its K48-linked polyubiquitination.
- Stabilized MYH9 activates the AKT/BAD signaling axis, suppressing apoptosis and driving lenvatinib resistance.
- Targeting the ETS1/USP43/MYH9 axis could be a therapeutic strategy to overcome lenvatinib resistance in HCC.