ArticleCell death & disease2025
USP28 promotes PARP inhibitor resistance by enhancing SOX9-mediated DNA damage repair in ovarian cancer.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Tropomyosin-1 positively regulates TGF-β/Smad3 signaling through STUB1 in arecoline-induced oral submucosal fibrosis.Odontology · 2026Article
- Ubiquitin-specific proteases in ovarian cancer: molecular mechanisms and therapeutic implications.Journal of ovarian research · 2026Review
- RILPL2 suppresses metabolic reprogramming and progression of cervical cancer by attenuating LDHA protein stability and inhibiting H3K18 lactylation.Cell death & disease · 2026Article
- Article
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Terpenoids: Emerging Natural Modulators for Reversing ABC Transporter-Mediated Multidrug Resistance in Cancer Chemotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Biomembrane-coated Nanoparticles Targeting circHIF1α Suppress Ovarian Cancer Metastasis and Cisplatin Resistance by Mediating System Xc⁻ Inactivation via SLC7A11/SLC3A2 to Induce Ferroptosis in Cancer Stem Cells.International journal of biological sciences · 2026Article
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- Mechanisms of resistance to PARP inhibitors in advanced epithelial ovarian cancer: biological determinants and therapeutic implications.Frontiers in oncology · 2026Review
- Targeting the deubiquitinase USP28 in cancer: navigating context-dependent mechanisms and therapeutic resistance.Frontiers in immunology · 2026Review
- In silico functional, structural, and pathogenicity assessment of single nucleotide polymorphisms in the human SOX9 gene.Scientific reports · 2025Article
- USP44 promotes chemotherapeutic drug resistance of triple negative breast cancer through EZH2 protein stability.Cancer biology & therapy · 2025Article
- Drug resistance in cancer: molecular mechanisms and emerging treatment strategies.Molecular biomedicine · 2025Review
- Super-enhancer inhibitors THZ2 and JQ1 reverse temozolomide resistance in glioblastoma by suppressing SE-driven SOX9 expression.Cancer drug resistance (Alhambra, Calif.) · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
PARP inhibitor (PARPi) resistance presents a significant challenge in ovarian cancer treatment, necessitating the development of effective therapeutic strategies to overcome this resistance and improve patient outcomes. Our study demonstrated that elevated expression of SRY-box 9 (SOX9) contributes to olaparib resistance in ovarian cancer. Mechanistically, the deubiquitinating enzyme USP28 was identified as a novel interacting partner of SOX9. USP28 inhibited the ubiquitination and subsequent degradation of SOX9, which is mediated by the E3 ubiquitin ligase FBXW7 during olaparib treatment. ChIP-Seq analysis revealed that SOX9 binds to the promoters of key DNA damage repair (DDR) genes (SMARCA4, UIMC1, and SLX4), thereby regulating DDR processes in ovarian cancer. Additionally, USP28 promoted olaparib resistance by stabilizing SOX9 protein and enhancing DNA damage repair. Furthermore, the USP28 specific inhibitor AZ1 reduced SOX9 protein stability and increased the sensitivity of ovarian cancer cells to olaparib. In conclusion, targeted inhibition of USP28 promoted ubiquitination-mediated degradation of SOX9, thereby impairing DNA damage repair capabilities and sensitizing ovarian cancer cells to PARPi. These findings elucidate the underlying mechanisms of PARPi resistance in ovarian cancer and suggest the potential efficacy of combining USP28 inhibitors with PARPi to overcome this resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.