ArticleJournal of experimental & clinical cancer research : CR2021
Lnc-RP11-536 K7.3/SOX2/HIF-1α signaling axis regulates oxaliplatin resistance in patient-derived colorectal cancer organoids.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Inhibition of TLR4 enhances oxaliplatin chemotherapy sensitivity in esophageal squamous cell carcinoma by suppressing inflammation and glycolysis.BMC gastroenterology · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Review
- Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.Chemical reviews · 2025Review
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- Precision medicine research progress based on colorectal cancer organoids.Discover oncology · 2025Review
- PWRN1 low expression facilitates cancer progression and is an unfavorable prognosis factor in breast cancer.Discover oncology · 2025Article
- Targeting ncRNAs to overcome metabolic reprogramming‑mediated drug resistance in cancer (Review).International journal of oncology · 2025Review
- CSF2 promotes chemoresistance in colorectal cancer by regulating Notch pathway.Discover oncology · 2025Article
- Interactions Between Non-Coding RNAs and HIF-1alpha in the Context of Colorectal Cancer.Biomolecules · 2025Review
- NAD+/SIRT1 pathway regulates glycolysis to promote oxaliplatin resistance in colorectal cancer.World journal of gastroenterology · 2025Article
- Exploring the Link Between Noncoding RNAs and Glycolysis in Colorectal Cancer.Journal of cellular and molecular medicine · 2025Review
- Anti-tumor role and molecular mechanism of vanillic acid.Discover oncology · 2025Review
- Modeling methods of different tumor organoids and their application in tumor drug resistance research.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Macrophage Tim-4 protects against deep vein thrombosis by binding CK2β to suppress inflammatory responses.Frontiers in immunology · 2025Article
- Combined Oxaliplatin with 5-Fluorouracil for Effective Chemotherapy Against Gastric Cancer in Animal Model.International journal of nanomedicine · 2025Article
- Ginsenoside potential targeting hypoxia-inducible factor-1α as promising therapeutics for cancer: a review.Frontiers in medicine · 2025Review
- Ubiquitin-specific protease 7 maintains c-Myc stability to support pancreatic cancer glycolysis and tumor growth.Journal of translational medicine · 2024Article
- Exploring the role of tRNA-derived small RNAs (tsRNAs) in disease: implications for HIF-1 pathway modulation.Journal of molecular medicine (Berlin, Germany) · 2024Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundResistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet.
methodsChemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α.
resultsIn this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin.
conclusionIn conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.
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