ArticlePloS one2011
G4-DNA formation in the HRAS promoter and rational design of decoy oligonucleotides for cancer therapy.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 110 citations in OpenAlex.
- Structure-Informed Design of Distinct Parallel G-Quadruplex Stabilizers for KRAS-Driven Cancer Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- RNA G-quadruplex structure recognition by chimeric peptides.Nucleic acids research · 2026Article
- RBM5 Acts as a Tumor Suppressor in Breast Cancer Through Binding to G-quadruplexes in the BAP1 Gene Promoter to Activate Its Expression.Molecules (Basel, Switzerland) · 2026Article
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Tripodal Quinone-Cyanine G-Quadruplex Ligands as Novel Photosensitizers on Photoinduced Cancer Cell Death.Molecules (Basel, Switzerland) · 2024Article
- Unlocking the potential of protein-derived peptides to target G-quadruplex DNA: from recognition to anticancer activity.Nucleic acids research · 2024Article
- Estrone-Based Derivatives Stabilize theACS omega · 2024Article
- G-Quadruplexes in the Regulation of Viral Gene Expressions and Their Impacts on Controlling Infection.Pathogens (Basel, Switzerland) · 2024Review
- 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification.Experimental & molecular medicine · 2022Review
- CpG Methylation Altered the Stability and Structure of the i-Motifs Located in the CpG Islands.International journal of molecular sciences · 2022Article
- G4-quadruplex-binding proteins: review and insights into selectivity.Biophysical reviews · 2022Review
- Detection of CpG Methylation in G-Quadruplex Forming Sequences Using G-Quadruplex Ligands.International journal of molecular sciences · 2021Article
- Identification of the transcription factor MAZ as a regulator of erythropoiesis.Blood advances · 2021Article
- Beyond small molecules: targeting G-quadruplex structures with oligonucleotides and their analogues.Nucleic acids research · 2021Review
- DNA G-Quadruplexes Contribute to CTCF Recruitment.International journal of molecular sciences · 2021Article
- G-quadruplexes: a promising target for cancer therapy.Molecular cancer · 2021Review
- G-quadruplex-forming nucleic acids interact with splicing factor 3B subunit 2 and suppress innate immune gene expression.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
- Article
- Review
- On the epigenetic role of guanosine oxidation.Redox biology · 2020Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HRAS is a proto-oncogene involved in the tumorigenesis of urinary bladder cancer. In the HRAS promoter we identified two G-rich elements, hras-1 and hras-2, that fold, respectively, into an antiparallel and a parallel quadruplex (qhras-1, qhras-2). When we introduced in sequence hras-1 or hras-2 two point mutations that block quadruplex formation, transcription increased 5-fold, but when we stabilized the G-quadruplexes by guanidinium phthalocyanines, transcription decreased to 20% of control. By ChIP we found that sequence hras-1 is bound only by MAZ, while hras-2 is bound by MAZ and Sp1: two transcription factors recognizing guanine boxes. We also discovered by EMSA that recombinant MAZ-GST binds to both HRAS quadruplexes, while Sp1-GST only binds to qhras-1. The over-expression of MAZ and Sp1 synergistically activates HRAS transcription, while silencing each gene by RNAi results in a strong down-regulation of transcription. All these data indicate that the HRAS G-quadruplexes behave as transcription repressors. Finally, we designed decoy oligonucleotides mimicking the HRAS quadruplexes, bearing (R)-1-O-[4-(1-Pyrenylethynyl) phenylmethyl] glycerol and LNA modifications to increase their stability and nuclease resistance (G4-decoys). The G4-decoys repressed HRAS transcription and caused a strong antiproliferative effect, mediated by apoptosis, in T24 bladder cancer cells where HRAS is mutated.
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