O-GlcNAcylation of UBAP2L regulates stress granule formation and sunitinib resistance in clear cell renal cell carcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.UBAP2L O-GlcNAcylation enhances sunitinib resistance in clear cell renal cell carcinoma (ccRCC) by stabilizing UBAP2L and promoting stress granule formation. This finding offers new therapeutic targets for ccRCC treatment.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Sunitinib resistance significantly worsens clear cell renal cell carcinoma (ccRCC) prognosis.
- Stress granules (SGs) contribute to tumor cell adaptation and drug resistance in various cancers.
Purpose Of The Study
- To investigate the mechanisms of sunitinib resistance in ccRCC.
- To identify key mediators of drug resistance.
- To explore the role of UBAP2L and its O-GlcNAcylation in ccRCC progression and resistance.
Main Methods
- Developed sunitinib-resistant patient-derived xenograft (PDX) and organoid (PDO) models for ccRCC.
- Utilized proteomic analysis to identify UBAP2L as a key mediator.
- Conducted in vitro and in vivo studies, including immunoprecipitation, mass spectrometry, RNA-seq, and RIP-seq, to elucidate regulatory mechanisms.
Main Results
- UBAP2L enrichment correlated with sunitinib-resistant ccRCC PDX models.
- UBAP2L protected ccRCC from apoptosis, promoted proliferation and angiogenesis, enhancing drug resistance.
- UBAP2L O-GlcNAcylation enhanced protein stability by inhibiting TRIM37-mediated ubiquitination, regulated SGs, increased Melk mRNA stability, and activated PI3K signaling.
Conclusions
- O-GlcNAcylation of UBAP2L plays a significant role in ccRCC sunitinib resistance.
- This study provides a novel theoretical foundation for clinical diagnosis and therapy of ccRCC.
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