ArticleMolecular cancer2022
circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Diagnostic and prognostic role of circRNAs in pancreatic cancer: a meta-analysis.Frontiers in oncology · 2023Pooled it
- The regulatory roles of non-coding RNAs in aerobic glycolysis and therapeutic potential in pancreatic ductal adenocarcinoma.Annals of medicine · 2026Review
- Construction of a Glutathione-Gated Intelligent Nanoclassifier for Spatioselective Visualization of Dual CircRNAs and Synergistic Photodynamic Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- Lactate derived from CAFs mediates H3K18la in stemness gene promoters, which promotes tumor malignant phenotype formation.Molecular genetics and genomics : MGG · 2026Article
- m6A Modification-Mediated LINC01547 Promotes Pancreatic Cancer Growth and Gemcitabine Resistance Through miR-34a-5p/MYH9 Axis.Biochemical genetics · 2026Article
- circFOXP1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Regulating EREG/MAPK/ERK Axis.Journal of cellular and molecular medicine · 2026Article
- Hsa_circ_0007158 promotes colorectal cancer progression via the ceRNA axis and its association with immune infiltration.Cancer cell international · 2026Article
- Research progress of plant-derived chemical compounds for overcoming pancreatic cancer drug resistance.World journal of gastroenterology · 2026Review
- CircRNAs: Novel biomarkers and therapeutic targets for diseases of the central nervous system.Biochemistry and biophysics reports · 2026Review
- Alternative splicing in cancer drug resistance: Mechanisms and therapeutic prospects (Review).Oncology reports · 2026Review
- Circular RNA hsa_circ_0001829 promotes pancreatic ductal adenocarcinoma through miR-7113-3p/DTX4 axis.World journal of surgical oncology · 2026Article
- Whole-transcriptome sequencing reveals hypoxic esophageal squamous cell carcinoma-derived migrasomes driving cancer-associated fibroblast activation.Briefings in functional genomics · 2026Article
- Novel anti-tumor strategies: targeting the crosstalk between cancer stem cells and cancer-associated fibroblasts to resist drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- CAF-derived exosomal circMPP6 drives ovarian cancer metastasis by coordinating nuclear and cytoplasmic regulation of ADAM22 to activate TGF-β/Smad signaling.International journal of biological sciences · 2026Article
- KRAS-driven cytokine-metabolic crosstalk shapes immune exclusion in pancreatic ductal adenocarcinoma.Frontiers in genetics · 2026Review
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- Impact of pancreatic proenzymes on pancreatic ductal adenocarcinoma associated fibroblasts.Scientific reports · 2025Article
- Cancer-associated fibroblast-derived circKLHL24 drives perineural invasion in pancreatic cancer via dual regulation of the sec31a-CXCL12 axis.Journal of experimental & clinical cancer research : CR · 2025Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer-associated fibroblasts (CAFs) are critically involved in gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanism by which CAFs promote chemotherapy resistance remains unexplored. Here, we explored the role of circRNAs in CAF-induced GEM resistance in PDAC.
methodscircRNA sequencing and quantitative real-time PCR (qRT-PCR) were utilized to screen CAF-specific circRNAs. The effects of CAF circFARP1 expression on GEM resistance in tumor cells were assessed in vitro and in vivo. RNA-seq, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays were used to screen the downstream target and underlying mechanism of circFARP1.
resultscircFARP1 (hsa_circ_0002557), a CAF-specific circRNA, was positively correlated with GEM chemoresistance and poor survival in an advanced PDAC cohort. Silencing or overexpressing circFARP1 in CAFs altered the ability of CAFs to induce tumor cell stemness and GEM resistance via leukemia inhibitory factor (LIF). Mechanistically, we found that circFARP1 directly binds with caveolin 1 (CAV1) and blocks the interaction of CAV1 and the E3 ubiquitin-protein ligase zinc and ring finger 1 (ZNRF1) to inhibit CAV1 degradation, which enhances LIF secretion. In addition, circFARP1 upregulated LIF expression by sponging miR-660-3p. Moreover, high circFARP1 levels were positively correlated with elevated serum LIF levels in PDAC and poor patient survival. Decreasing circFARP1 levels and neutralizing LIF significantly suppressed PDAC growth and GEM resistance in patient-derived xenograft models.
conclusionsThe circFARP1/CAV1/miR-660-3p/LIF axis is critical for CAF-induced GEM resistance in PDAC. Hence, circFARP1 may be a potential therapeutic target for PDAC.
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