ArticleMolecular cancer2022
CircRTN4 promotes pancreatic cancer progression through a novel CircRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein.
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 67 papers, 2 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Risk SNP in a transcript of RP11-638I2.4 increases lncRNA-YY1 interaction and pancreatic cancer susceptibility.Archives of toxicology · 2023Pooled it
- Diagnostic and prognostic role of circRNAs in pancreatic cancer: a meta-analysis.Frontiers in oncology · 2023Pooled it
- Pancreatic cancer EMT‑targeted therapy: Molecular mechanisms and clinical translation (Review).International journal of oncology · 2026Review
- Circular RNA hsa_circ_0003472 Promotes Pancreatic Ductal Adenocarcinoma Progression and Gemcitabine Resistance Via the mir-1253/ERCC1 Axis.Biological procedures online · 2026Article
- Non-coding RNAs: modulators of signaling pathways and prognostic biomarkers in digestive system cancer.Molecular cancer · 2026Review
- Research progress on early diagnostic markers for pancreatic cancer.World journal of surgical oncology · 2026Review
- Mechanistic insights into hepatic metastasis of pancreatic cancer: molecular perspectives.Translational gastroenterology and hepatology · 2026Review
- Long non-coding RNAs: Emerging regulators of invasion and metastasis in pancreatic cancer.Journal of advanced research · 2025Review
- Recent advances in hydrogel-based delivery systems for the treatment of pancreatic cancer.Materials today. Bio · 2025Review
- Hyperoside, a flavonoid, inducesScience advances · 2025Article
- Review
- The diverse roles of circular RNAs in cholangiocarcinoma.Medical oncology (Northwood, London, England) · 2025Review
- An interplay of non-coding RNAs regulatesResearch square · 2025Article
- CircRNAs: functions and emerging roles in cancer and immunotherapy.BMC medicine · 2025Review
- circGIGYF1 inhibits stemness and metastasis in colorectal cancer by promoting WWP2-HOXD13 interaction to regulate β-catenin signalling.Communications biology · 2025Article
- UBE3C promotes pancreatic ductal adenocarcinoma progression by catalysing p53 ubiquitination.Molecular biology reports · 2025Article
- Advances in the application of extracellular vesicles in precise diagnosis of pancreatic cancer.European journal of medical research · 2025Review
- Biological functions and molecular mechanisms of circHIPK3 in digestive system tumors.Human cell · 2025Review
- Role of noncoding RNA and protein interaction in pancreatic cancer.Chinese medical journal · 2025Review
- Depletion of the RNA binding protein QKI and circular RNA dysregulation in T-cell acute lymphoblastic leukemia.Haematologica · 2025Article
7 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCircular RNAs (circRNAs) play important roles in many biological processes. However, the detailed mechanism underlying the critical roles of circRNAs in cancer remains largely unexplored. We aim to explore the molecular mechanisms of circRTN4 with critical roles in pancreatic ductal adenocarcinoma (PDAC).
methodsCircRTN4 expression level was examined in PDAC primary tumors. The oncogenic roles of circRTN4 in PDAC tumor growth and metastasis were studied in mouse tumor models. Bioinformatics analysis, luciferase assay and miRNA pulldown assay were performed to study the novel circRTN4-miRNA-lncRNA pathway. To identify circRTN4-interacting proteins, we performed circRNA-pulldown and mass spectrometry in PDAC cells. Protein stability assay and 3-Dimensional structure modeling were performed to reveal the role of circRTN4 in stabilizing RAB11FIP1.
resultsCircRTN4 was significantly upregulated in primary tumors from PDAC patients. In vitro and in vivo functional studies revealed that circRTN4 promoted PDAC tumor growth and liver metastasis. Mechanistically, circRTN4 interacted with tumor suppressor miR-497-5p in PDAC cells. CircRTN4 knockdown upregulated miR-497-5p to inhibit the oncogenic lncRNA HOTTIP expression. Furthermore, we identified critical circRTN4-intercting proteins by circRNA-pulldown in PDAC cells. CircRTN4 interacted with important epithelial-mesenchymal transition (EMT)- driver RAB11FIP1 to block its ubiquitination site. We found that circRTN4 knockdown promoted the degradation of RAB11FIP1 by increasing its ubiquitination. Also, circRTN4 knockdown inhibited the expression of RAB11FIP1-regulating EMT-markers Slug, Snai1, Twist, Zeb1 and N-cadherin in PDAC.
conclusionThe upregulated circRTN4 promotes tumor growth and liver metastasis in PDAC through the novel circRTN4-miR-497-5p-HOTTIP pathway. Also, circRTN4 stabilizes RAB11FIP1 to contribute EMT.
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