ArticleJournal of experimental & clinical cancer research : CR2022
circCUL2 induces an inflammatory CAF phenotype in pancreatic ductal adenocarcinoma via the activation of the MyD88-dependent NF-κB signaling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Diagnostic and prognostic role of circRNAs in pancreatic cancer: a meta-analysis.Frontiers in oncology · 2023Pooled it
- Circular RNAs in tumorigenesis: an insight into recent research in biogenesis and targeted tumor therapy.Cell cycle (Georgetown, Tex.) · 2026Review
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- Remodeling the Stroma: The Role of ncRNAs in Cancer-Associated Fibroblasts and Therapeutic Implications for Digestive Tumors.Drug design, development and therapy · 2026Review
- Circular RNAs: Fundamental mechanisms in tumor metastasis and detection strategies (Review).Molecular medicine reports · 2025Review
- 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
- Decoding the functional roles of circular RNAs linked to NF-κB pathway in carcinogenesis.Discover oncology · 2025Review
- CircERC1 facilitates chemoresistance through inhibiting pyroptosis and remodeling extracellular matrix in pancreatic cancer.Molecular cancer · 2025Article
- Decoding the pancreatic cancer microenvironment: The multifaceted regulation of microRNAs.Clinical and translational medicine · 2025Review
- PPY-Induced iCAFs Cultivate an Immunosuppressive Microenvironment in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation.Cell death & disease · 2025Article
- Inflammation, microbiota, and pancreatic cancer.Cancer cell international · 2025Review
- Circular RNAs in cancer.MedComm · 2025Review
- Benign non-immune cells in tumor microenvironment.Frontiers in immunology · 2025Review
- Biological roles and molecular mechanism of circular RNAs in epithelial-mesenchymal transition of gastrointestinal malignancies.Oncology research · 2025Review
- Circular RNA in Pancreatic Cancer: Biogenesis, Mechanism, Function and Clinical Application.International journal of medical sciences · 2025Review
- Exosomes containing circSCP2 in colorectal cancer promote metastasis via sponging miR-92a-1-5p and interacting with PTBP1 to stabilize IGF2BP1.Biology direct · 2024Article
- Interplay between JAK/STAT pathway and non-coding RNAs in different cancers.Non-coding RNA research · 2024Review
- Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution.Journal of hematology & oncology · 2024Review
- Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy.Cancer metastasis reviews · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is characterized by clusters of cancer cells surrounded by a dense desmoplastic stroma. However, little is known about stromal cell heterogeneity in the pancreatic tumor microenvironment.
methodsWe conducted circRNA profiling in primary fibroblasts by high-throughput sequencing and detected circCUL2 levels in PDAC tissues by qRT-PCR. We subsequently investigated the effect of circCUL2 on inflammatory cancer-associated fibroblast (iCAF) activation, heterogeneity and protumor activity by ELISA, flow cytometry, colony formation and transwell assays in vitro and by xenograft models in vivo. The regulatory effect of circCUL2 on miR-203a-3p/MyD88/IL6 was examined by RNA pulldown, FISH, and luciferase reporter assays.
resultsWe identified that circCUL2 was specifically expressed in cancer-associated fibroblasts (CAFs) but not in cancer cells. Moreover, the enrichment of circCUL2 in tumor tissues was significantly correlated with the poor prognosis of PDAC patients. Upregulation of circCUL2 expression in normal fibroblasts (NFs) induced the iCAF phenotype, and then iCAFs promoted PDAC progression through IL6 secretion in vitro. Furthermore, circCUL2-transduced NFs promoted tumorigenesis and metastasis of PDAC cells in vivo, which was blocked by an anti-IL6 antibody. Mechanistically, circCUL2 functioned as a ceRNA and modulated the miR-203a-3p/MyD88/NF-κB/IL6 axis, thereby further activating the STAT3 signaling pathway in pancreatic cancer cells to induce PDAC progression.
conclusionsWe showed that the circCUL2/miR-203a-5p/MyD88/NF-κB/IL6 axis contributes to the induction of iCAFs and established a distinct fibroblast niche for PDAC progression, which could help the development of strategies that selectively target tumor-promoting CAFs in PDAC.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.