ArticleNucleic acids research2022
The human AP-endonuclease 1 (APE1) is a DNA G-quadruplex structure binding protein and regulates KRAS expression in pancreatic ductal adenocarcinoma cells.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 58 citations in OpenAlex.
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- In vivo dynamics of G-quadruplex DNA structures during liver regeneration in mice.Scientific reports · 2026Article
- Endogenous promoter G-quadruplexes scaffold apurinic/apyrimidinic endonuclease (APE1) to drive gene expression.Nucleic acids research · 2026Article
- Piperine alleviates retinal ischemic injury by mediating the APE1 signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.Research (Washington, D.C.) · 2026Review
- Base excision repair within structure-forming repeat sequences and its impact on cancer and other diseases.NAR cancer · 2025Review
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- The Hippo-YAP signaling pathway promotes hepatocellular carcinoma progression by inducing FHL3 expression.Cell death & disease · 2025Article
- The Zuo1 C-terminal domain stabilizes DNA guanosine quadruplex (G4) structures located on Chromosome IX in Saccharomyces cerevisiae.Nucleic acids research · 2025Article
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- The Relevance of G-Quadruplexes in Gene Promoters and the First Introns Associated with Transcriptional Regulation in Breast Cancer.International journal of molecular sciences · 2025Article
- DNA 5mC methylation inhibits the formation of G-quadruplex structures in the genome.Genome biology · 2025Article
- APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism.iScience · 2025Article
- Decoding G-Quadruplexes Sequence inPlants (Basel, Switzerland) · 2025Article
- APE1 condensation in nucleoli of non-cancer cells depends on rRNA transcription and forming G-quadruplex RNA structures.Nucleic acids research · 2025Article
- Position-Dependent Effects of AP Sites Within anInternational journal of molecular sciences · 2025Article
- Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.Protein and peptide letters · 2025Review
- Profiling of i-motif-binding proteins reveals functional roles of nucleolin in regulation of high-order DNA structures.Nucleic acids research · 2024Article
- Review
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9 authors at 1 institution in 1 country.
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Abstract
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive types of cancer, is characterized by aberrant activity of oncogenic KRAS. A nuclease-hypersensitive GC-rich region in KRAS promoter can fold into a four-stranded DNA secondary structure called G-quadruplex (G4), known to regulate KRAS expression. However, the factors that regulate stable G4 formation in the genome and KRAS expression in PDAC are largely unknown. Here, we show that APE1 (apurinic/apyrimidinic endonuclease 1), a multifunctional DNA repair enzyme, is a G4-binding protein, and loss of APE1 abrogates the formation of stable G4 structures in cells. Recombinant APE1 binds to KRAS promoter G4 structure with high affinity and promotes G4 folding in vitro. Knockdown of APE1 reduces MAZ transcription factor loading onto the KRAS promoter, thus reducing KRAS expression in PDAC cells. Moreover, downregulation of APE1 sensitizes PDAC cells to chemotherapeutic drugs in vitro and in vivo. We also demonstrate that PDAC patients' tissue samples have elevated levels of both APE1 and G4 DNA. Our findings unravel a critical role of APE1 in regulating stable G4 formation and KRAS expression in PDAC and highlight G4 structures as genomic features with potential application as a novel prognostic marker and therapeutic target in PDAC.
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