ArticleRNA biology2015
Stabilization of the G-quadruplex at the VEGF IRES represses cap-independent translation.
Article in RNA biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 74 citations in OpenAlex.
- Cap-Independent Translation Regulation of VEGF Using CRISPR-dCas13d.bioRxiv : the preprint server for biology · 2026Article
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Intrinsically disordered SERBP1 regulates translation through topology-driven G-quadruplex recognition.bioRxiv : the preprint server for biology · 2026Article
- RNA G-quadruplexes in oncogene regulation and as emerging targets for cancer therapy.Cell communication and signaling : CCS · 2026Review
- Stability of non-canonical nucleic acid structure as a potential modulator of cell fate.Nucleic acids research · 2026Review
- Integrating rna structure and protein interactions to uncover the mechanisms of viral and cellular ires function.Biology direct · 2025Article
- RNA G‑Quadruplex Reprogramming with Guanine-Rich Antisense Oligonucleotides Inhibits Monoamine Oxidase B's Translation.ACS bio & med chem Au · 2025Article
- G-Quadruplexes in Tumor Immune Regulation: Molecular Mechanisms and Therapeutic Prospects in Gastrointestinal Cancers.Biomedicines · 2025Review
- Conformational Propensities of a DNA Hairpin with a Stem Sequence from the c-MYC Promoter.Biomolecules · 2025Article
- Untranslated region engineering strategies for gene overexpression, fine-tuning, and dynamic regulation.Journal of microbiology (Seoul, Korea) · 2025Review
- PERK-Olating Through Cancer: A Brew of Cellular Decisions.Biomolecules · 2025Review
- 5'-UTR G-Quadruplex-Mediated Translation Regulation in Eukaryotes: Current Understanding and Methodological Challenges.International journal of molecular sciences · 2025Review
- Design and characterization of G-quadruplex RNA aptamers reveal RNA-binding by KDM5 lysine demethylases.Computational and structural biotechnology journal · 2025Article
- The crosstalk between metabolism and translation.Cell metabolism · 2024Review
- The shaping of mRNA translation plasticity by RNA G-quadruplexes in cancer progression and therapy resistance.NAR cancer · 2024Review
- 5'UTR G-quadruplex structure enhances translation in size dependent manner.Nature communications · 2024Article
- G-Quadruplex Structures Are Key Modulators of Somatic Structural Variants in Cancers.Cancer research · 2023Article
- Aberrant splicing in human cancer: An RNA structural code point of view.Frontiers in pharmacology · 2023Review
- Interaction between non-coding RNAs, mRNAs and G-quadruplexes.Cancer cell international · 2022Review
- How VEGF-A and its splice variants affect breast cancer development - clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of translation contributes to malignant transformation and is an emerging target for cancer therapies. RNA G-quadruplex structures are general inhibitors of cap-dependent mRNA translation and were recently shown to be targeted for oncoprotein translational activation. In contrast however, the G-quadruplex within the 5'UTR of the human vascular endothelial growth factor A (VEGF) has been shown to be essential for IRES-mediated translation. Since VEGF has a pivotal role in tumor angiogenesis and is a major target of anti-tumoral therapies, we investigated the structure/function relationship of the VEGF G-quadruplex and defined whether it could have a therapeutic potential. We found that the G-quadruplex within the VEGF IRES is dispensable for cap-independent function and activation in stress conditions. However, stabilization of the VEGF G-quadruplex by increasing the G-stretches length or by replacing it with the one of NRAS results in strong inhibition of IRES-mediated translation of VEGF. We also demonstrate that G-quadruplex ligands stabilize the VEGF G-quadruplex and inhibit cap-independent translation in vitro. Importantly, the amount of human VEGF mRNA associated with polysomes decreases in the presence of a highly selective stabilizing G-quadruplex ligand, resulting in reduced VEGF protein expression. Together, our results uncover the existence of functionally silent G-quadruplex structures that are susceptible to conversion into efficient repressors of cap-independent mRNA translation. These findings have implications for the in vivo applications of G-quadruplex-targeting compounds and for anti-angiogenic therapies.
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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.