ArticleMolecular cancer2025
CircERC1 facilitates chemoresistance through inhibiting pyroptosis and remodeling extracellular matrix in pancreatic cancer.
Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- m6A-modified circFOXA1 promotes tumor immune evasion via enhancing PD-L1 deubiquitination in triple-negative breast cancer.Cytotechnology · 2026Article
- CDKN1A promotes paclitaxel resistance through mediating formation of polyploid giant cancer cells and enhancing neosis in non-small cell lung cancer.Translational lung cancer research · 2026Article
- Extracellular vesicles as regulators of chemotherapy resistance in oral squamous cell carcinoma.Discover oncology · 2026Review
- Organ-Specific Migration License (OSML) theory: a novel paradigm for spatiotemporal regulation and intervention of cross-organ immune cell migration in tumor immune responses.Cell communication and signaling : CCS · 2026Review
- Extracellular vesicles as modulators of cancer metabolism and microenvironment.Extracellular vesicles and circulating nucleic acids · 2026Review
- Recent advances in research on the multifactorial mechanisms underlying paclitaxel resistance and translational intervention strategies.Frontiers in pharmacology · 2026Review
- Inflammasome-associated pyroptosis and tumor angiogenesis in prostate cancer.Iranian journal of basic medical sciences · 2026Review
- Integrated single-cell and bulk transcriptomic analyses reveal cDC1-centered ubiquitination dysregulation and identify UBE2F as a critical regulator in sepsis.Frontiers in immunology · 2026Article
- IL1RAJournal of clinical and translational hepatology · 2025Article
- Circular RNAs: key regulators of paclitaxel sensitivity and resistance in cancer.European journal of medical research · 2025Review
- The role of circRNAs in NScience progressReview
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14 authors.
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Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) resists to neoadjuvant treatment even though overall survival (OS) is transiently prolonged while the underlying mechanism of this drug resistance remains elusive.
methodsGemcitabine combined with Nab-paclitaxel (GEM-NabP) treated PDAC tissues-derived EVs were isolated and underwent circRNA sequencing. CircERC1 was identified as an EVs-packaged circRNA that regulates PDAC progression and tumor microenvironment (TME) in vitro and in vivo with the help of EdU, colony formation, SRB viability assays, transwell assays and PET-CT analysis. The underlying mechanism was substantiated by qRT-PCR, Western blot, RNA pull-down, mass spectrometry, RNA immunoprecipitation and Co-immunoprecipitation. In addition, single-cell RNA sequencing was adopted to analyze the TME and immunohistochemistry, dual luciferase reporter assay were performed to validate the results.
resultsCircERC1 biogenesis is activated by QKI after GEM-NabP treatment. It interacts with hnRNPA1 and promotes its ubiquitination degradation by blocking its SUMOylation at K183. The degraded hnRNPA1 fails to upregulate PKM2, a crucial activator of NLRP3 inflammasome, thereby inhibiting Caspase1-GSDMD mediated pyroptosis. Furthermore, EVs-packaged circERC1 enhances extracellular matrix (ECM) deposition and hindering drug and immune cells infiltration in cancer associated fibroblasts (CAFs) in PDAC microenvironment.
conclusionsOur findings reveal a novel circERC1 as a key regulator in PDAC-secreted EVs following paclitaxel (PTX) treatment, thereby inhibiting gemcitabine/Nab-paclitaxel (GEM-NabP) induced pyroptosis. Our results highlight a potential therapeutic target for overcoming chemoresistance and remodeling pancreatic TME.
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