ArticleCell death & disease2025
STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis.
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.
- The versatile roles of long non-coding RNAs in kidney disease.Nature reviews. Nephrology · 2026Review
- Integrated OAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulatory networks of non-coding RNAs in renal cell carcinogenesis and therapeutic intervention strategies.World journal of urology · 2026Review
- Mitochondrial Carrier SLC25A13 Drives Ferroptosis Resistance and Immune Evasion via a STAT3-IFI6 Circuit in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Long Non-Coding RNAs in Pathogenesis of Renal Cell Carcinoma: Epigenetic Regulation, Signaling Pathways, and Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Non-coding RNAs as master regulators of ferroptosis in cancer: mechanisms and clinical implications.Molecular cancer · 2026Review
- Anti-cancer effect of palmitic acid against the endometrial cancer progression via inducing ferroptosis.Biochemistry and biophysics reports · 2026Article
- Short and Long Non-Coding RNAs in Renal Cell Carcinoma.Non-coding RNA · 2026Review
- Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer.Biomedicines · 2026Review
- Integrating machine learning and multi-omics analysis to explore Treg-associated programmed cell death features in clear cell renal cell carcinoma.Cancer cell international · 2026Article
- The role of ferroptosis in renal cell carcinoma: molecular mechanisms and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Screening of PANoptosis regulator-associated long noncoding RNAs and construction of a survival prognostic model in cutaneous melanoma.Translational cancer research · 2025Article
- Review
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
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Authors and funding
10 authors.
Funding
Abstract
Axitinib resistance remains a serious challenge in the treatment of advanced renal cell carcinoma (RCC), and the underlying mechanisms are not fully understood. Here, we constructed an in vivo axitinib-resistant RCC model and identified the long non-coding RNA STX17-DT as a driver of therapy resistance in RCC. The expression of STX17-DT was significantly elevated in axitinib-resistant RCC cells and correlated with poorer prognosis in RCC patients. Elevated levels of STX17-DT contributed to the development of resistance to axitinib both in vitro and in vivo. Mechanistically, STX17-DT modulated the stability of IFI6 mRNA by recruiting and binding to hnRNPA1, leading to decreased accumulation of mitochondrial reactive oxygen species (ROS) and attenuated ferroptosis. Meanwhile, STX17-DT was packaged into extracellular vesicles through hnRNPA1, thus transmitting axitinib resistance to other cells. Compared with axitinib monotherapy, combined treatment of axitinib and STX17-DT-targeted in vivo siRNA demonstrated enhanced therapeutic efficacy. These findings indicate a novel molecular mechanism of axitinib resistance in RCC and suggest that STX17-DT may serve as a prognostic indicator and potential therapeutic target to overcome resistance to targeted therapy.
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