ArticleOncogene2021
Hypoxic exosomal HIF-1α-stabilizing circZNF91 promotes chemoresistance of normoxic pancreatic cancer cells via enhancing glycolysis.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- Exosomal Non-Coding RNAs in Gastrointestinal Cancer Drug Resistance: A Systematic Review of Emerging Mechanisms and Clinical Implications.Journal of cellular and molecular medicine · 2026Pooled it
- EGFR-dependent delivery of phosphorylated IGFBP3 by cancer stem cells drives chemotherapy resistance in colorectal cancer.Cell death & disease · 2026Article
- Liquid Biopsy Frontiers in Pancreatic Cancer: Insights from Circulating Cell-Free Nucleic Acids.Cells · 2026Review
- The role of small extracellular vesicles in ovarian cancer drug resistance: from bench clues to clinical implications.Journal of ovarian research · 2026Review
- Review
- Tumor exosomes impact functional hallmarks of cancer.Cancer metastasis reviews · 2026Review
- Research progress of plant-derived chemical compounds for overcoming pancreatic cancer drug resistance.World journal of gastroenterology · 2026Review
- The possible role of sirtuins and MiRNAs in gastrointestinal cancers: special focus on Sirt1.Cancer cell international · 2026Review
- Hypoxic mesenchymal stem cell-Derived Exosomal circPTP4A2 improves granulosa cell mitochondrial function via YBX1.Cellular and molecular life sciences : CMLS · 2026Article
- Exosome-Mediated Regulation of Aerobic Glycolysis in Hepatocellular Carcinoma: Mechanisms and Therapeutic Implications.Journal of hepatocellular carcinoma · 2026Review
- ZFPL1 Promotes Colorectal Cancer Progression by Stabilizing ASS1 to Drive the Urea Cycle and M2 Macrophage-Mediated Metastatic Colonization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Diagnostic and therapeutic potential of exosomal circRNAs in cancer: decoding the circular code toward precision medicine.Cancer cell international · 2025Review
- Hypoxia-Induced Extracellular Vesicles and Non-Coding RNAs in Cancer: A Systematic Review of Tumor Dynamics and Therapeutic Implications in Preclinical Animal Models.Biomedicines · 2025Review
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Hypoxia-induced exosomal LUCAT1 promotes osimertinib resistance in lung adenocarcinoma by stabilizing c-MET.Cell death & disease · 2025Article
- CircRNAs: functions and emerging roles in cancer and immunotherapy.BMC medicine · 2025Review
- Exosome-mediated triple drug delivery enhances apoptosis in pancreatic cancer cells.Apoptosis : an international journal on programmed cell death · 2025Article
- Exosome-based approaches in cancer along with unlocking new insights into regeneration of cancer-prone tissues.Regenerative therapy · 2025Review
- Pathways and outputs orchestrated in tumor microenvironment cells by hypoxia-induced tumor-derived exosomes in pan-cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Exosome-Mediated Chemoresistance in Cancers: Mechanisms, Therapeutic Implications, and Future Directions.Biomolecules · 2025Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Research has indicated that hypoxia profoundly contributes to chemoresistance of pancreatic cancer (PC), while the precise mechanism has not been fully elucidated. In this study, we report a hypoxic exosomal circular RNA (circRNA)-mediated mechanism of conferred chemoresistance in PC cells. Gemcitabine (GEM) resistance was enhanced in normoxic PC cells incubated with exosomes derived from hypoxic PC cells. CircRNA microarray displayed that circZNF91 was remarkably increased in hypoxic exosomes of PC cells compared with normoxic exosomes. Overexpression of circZNF91 obviously stimulated chemoresistance in PC cells, while knockdown of circZNF91 retarded the hypoxic exosome-transmitted chemoresistance. Mechanistically, the hypoxic-induced exosomal circZNF91 transmitted into normoxic PC cells could competitively bind to miR-23b-3p, which deprives the inhibition of miR-23b-3p on expression of deacetylase Sirtuin1 (SIRT1). Consequently, the upregulated SIRT1 enhanced deacetylation-dependent stability of HIF-1α protein, leading to glycolysis and GEM chemoresistance of recipient PC cells. In addition, we revealed that the increased circZNF91 in hypoxic exosome was attributed to the transcriptional regulation by HIF-1α. Coincidently, transmission of hypoxic exosomes into subcutaneous xenografts in nude mice obviously facilitated the chemoresistance of transplanted PC tumor, which could be reversed by depletion of circZNF91 or upregulation of miR-23b-3p. Furthermore, clinical data showed that circZNF91 was significantly upregulated in PC tissues and correlated with overexpression of glycolytic enzymes and short overall survival time. Collectively, exosomal circZNF91 can function as a cargo mediating the signal transmission between hypoxic and normoxic tumor cells to promote GEM chemoresistance of PC and may potentially serve as a therapeutic target.
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Registered trials
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.