ArticleMolecular cancer2024
Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4-HDAC4-RUNX2-GAMT-mediated apoptosis.
Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Regulatory Effect of circRNA3890 on the Establishment of Receptive Endometrium in Dairy Goats.Animals : an open access journal from MDPI · 2026Article
- Recent advances of circular RNAs in gastrointestinal cancer.World journal of clinical oncology · 2025Review
- Advances in the research on circular RNA in pediatric pancreatic tumors.Translational pediatrics · 2025Review
- Role of noncoding RNA and protein interaction in pancreatic cancer.Chinese medical journal · 2025Review
- GAMT facilitates tumor progression via inhibiting p53 in clear cell renal cell carcinoma.Biology direct · 2025Article
- Epigenetic Regulation of Chromatin Functions by MicroRNAs and Long Noncoding RNAs and Implications in Human Diseases.Biomedicines · 2025Review
- A Circular RNA Promotes Tumor Metastasis through Stabilizing MSI2 Protein in Pancreatic Ductal Adenocarcinoma.Research (Washington, D.C.) · 2025Article
- The functional roles of deoxyelephantopin potential target circTNPO3 in regulating pancreatic cancer malignant phenotype and gemcitabine chemoresistance via miR-188-5p/CDCA3/TRAF2-mediated remodeling of NF-κB signaling pathway.Frontiers in pharmacology · 2025Article
- The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- The multifaceted regulatory roles of Nudix hydrolases in cancer and their therapeutic potential.Frontiers in oncology · 2025Review
- MicroRNAs in Pancreatic Cancer: Advances in Biomarker Discovery and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Roles and mechanisms of circular RNA in respiratory system cancers.Frontiers in oncology · 2024Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPancreatic cancer (PC) is an extremely malignant tumor with low survival rate. Effective biomarkers and therapeutic targets for PC are lacking. The roles of circular RNAs (circRNAs) in cancers have been explored in various studies, however more work is needed to understand the functional roles of specific circRNAs. In this study, we explore the specific role and mechanism of circ_0035435 (termed circCGNL1) in PC.
methodsqRT-PCR analysis was performed to detect circCGNL1 expression, indicating circCGNL1 had low expression in PC cells and tissues. The function of circCGNL1 in PC progression was examined both in vitro and in vivo. circCGNL1-interacting proteins were identified by performing RNA pulldown, co-immunoprecipitation, GST-pulldown, and dual-luciferase reporter assays.
resultsOverexpressing circCGNL1 inhibited PC proliferation via promoting apoptosis. CircCGNL1 interacted with phosphatase nudix hydrolase 4 (NUDT4) to promote histone deacetylase 4 (HDAC4) dephosphorylation and subsequent HDAC4 nuclear translocation. Intranuclear HDAC4 mediated RUNX Family Transcription Factor 2 (RUNX2) deacetylation and thereby accelerating RUNX2 degradation. The transcription factor, RUNX2, inhibited guanidinoacetate N-methyltransferase (GAMT) expression. GAMT was further verified to induce PC cell apoptosis via AMPK-AKT-Bad signaling pathway.
conclusionsWe discovered that circCGNL1 can interact with NUDT4 to enhance NUDT4-dependent HDAC4 dephosphorylation, subsequently activating HDAC4-RUNX2-GAMT-mediated apoptosis to suppress PC cell growth. These findings suggest new therapeutic targets for PC.
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