ArticleCancer research2023
Mutant KRAS Mediates circARFGEF2 Biogenesis to Promote Lymphatic Metastasis of Pancreatic Ductal Adenocarcinoma.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Pancreatic Lymphatics in Health and Disease: Evolution, Embryology, and Neural Control.Lymphatics · 2026Article
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Spatial transcriptomics reveals the mechanistic role of lactate metabolism in the pancreatic ductal adenocarcinoma microenvironment.Frontiers in immunology · 2026Article
- RNA-binding protein quaking: a multifunctional regulator in tumour progression.Annals of medicine · 2025Review
- CircPVT1 Promotes Lung Metastasis and Tumor Progression in Renal Cell Carcinoma by Encoding the cP104aa Peptide and Targeting EIF4A3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CircRNAs: functions and emerging roles in cancer and immunotherapy.BMC medicine · 2025Review
- CircERC1 facilitates chemoresistance through inhibiting pyroptosis and remodeling extracellular matrix in pancreatic cancer.Molecular cancer · 2025Article
- Role of noncoding RNA and protein interaction in pancreatic cancer.Chinese medical journal · 2025Review
- High-frequency KRAS mutations in pancreatic adenocarcinoma: prognostic significance and potential co-targeting therapies.Translational cancer research · 2025Article
- Targeting Regulatory Noncoding RNAs in Human Cancer: The State of the Art in Clinical Trials.Pharmaceutics · 2025Review
- EIF4E-mediated biogenesis of circPHF14 promotes the growth and metastasis of pancreatic ductal adenocarcinoma via Wnt/β-catenin pathway.Molecular cancer · 2025Article
- Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation.Cell death & disease · 2025Article
- CircRNA hsa_circ_0004781 promoted cell proliferation by acting as a sponge for miR-9-5p and miR-338-3p and upregulating KLF5 and ADAM17 expression in pancreatic ductal adenocarcinoma.Cancer cell international · 2025Article
- Article
- CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.Cellular & molecular biology letters · 2025Article
- Circular RNA in Pancreatic Cancer: Biogenesis, Mechanism, Function and Clinical Application.International journal of medical sciences · 2025Review
- RBMS1-mediates the biogenesis of circNFIB promotes perineural invasion of pancreatic ductal adenocarcinoma via the L1CAM/MAPK pathway.Theranostics · 2025Article
- RNA-Binding Proteins (RBPs) and Circular RNA Biogenesis.Advances in experimental medicine and biology · 2025Review
- Formation of Circular RNAs.Advances in experimental medicine and biology · 2025Review
- Interplay between JAK/STAT pathway and non-coding RNAs in different cancers.Non-coding RNA research · 2024Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Circular RNAs (circRNA) contribute to cancer stemness, proliferation, and metastasis. The biogenesis of circRNAs can be impacted by the genetic landscape of tumors. Herein, we identified a novel circRNA, circARFGEF2 (hsa_circ_0060665), which was upregulated in KRASG12D pancreatic ductal adenocarcinoma (PDAC) and positively associated with KRASG12D PDAC lymph node (LN) metastasis. CircARFGEF2 overexpression significantly facilitated KRASG12D PDAC LN metastasis in vitro and in vivo. Mechanistically, circARFGEF2 biogenesis in KRASG12D PDAC was significantly activated by the alternative splicing factor QKI-5, which recruited U2AF35 to facilitate spliceosome assembly. QKI-5 bound the QKI binding motifs and neighboring reverse complement sequence in intron 3 and 6 of ARFGEF2 pre-mRNA to facilitate circARFGEF2 biogenesis. CircARFGEF2 sponged miR-1205 and promoted the activation of JAK2, which phosphorylated STAT3 to trigger KRASG12D PDAC lymphangiogenesis and LN metastasis. Importantly, circARFGEF2 silencing significantly inhibited LN metastasis in the KrasG12D/+Trp53R172H/+Pdx-1-Cre (KPC) mouse PDAC model. These findings provide insight into the mechanism and metastasis-promoting function of mutant KRAS-mediated circRNA biogenesis. SIGNIFICANCE: Increased splicing-mediated biogenesis of circARFGEF2 in KRAS-mutant pancreatic ductal adenocarcinoma activates JAK2-STAT3 signaling and triggers lymph node metastasis, suggesting circARFGEF2 could be a therapeutic target to inhibit pancreatic cancer progression.
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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.