ArticleMolecular biology of the cell1999
Hypoxic regulation of vascular endothelial growth factor mRNA stability requires the cooperation of multiple RNA elements.
Article in Molecular biology of the cell, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 178 citations in OpenAlex.
- Beyond transcription: RNA-binding proteins steering angiogenesis.American journal of physiology. Heart and circulatory physiology · 2026Review
- Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells.Scientific reports · 2025Article
- Analysis of RNA Interference Targeted Against Human Antigen R (HuR) to Reduce Vascular Endothelial Growth Factor (VEGF) Protein Expression in Human Retinal Pigment Epithelial Cells.Molecular biotechnology · 2024Article
- Non-coding RNA regulatory networks in post-transcriptional regulation of VEGFA in cancer.IUBMB life · 2023Review
- Studying molecular signaling in major angiogenic diseases.Molecular and cellular biochemistry · 2022Review
- Pathophysiological Role of Genetic Factors Associated With Gestational Diabetes Mellitus.Frontiers in physiology · 2022Review
- VEGFR1 signaling in retinal angiogenesis and microinflammation.Progress in retinal and eye research · 2021Review
- Discrepancies on the Role of Oxygen Gradient and Culture Condition on Mesenchymal Stem Cell Fate.Advanced healthcare materials · 2021Review
- Angiogenic factors: role in esophageal cancer, a brief review.Esophagus : official journal of the Japan Esophageal Society · 2018Review
- Nuclear factor 90 promotes angiogenesis by regulating HIF-1α/VEGF-A expression through the PI3K/Akt signaling pathway in human cervical cancer.Cell death & disease · 2018Article
- A gapmer aptamer nanobiosensor for real-time monitoring of transcription and translation in single cells.Biomaterials · 2018Article
- The role of miR-106p-5p in cervical cancer: from expression to molecular mechanism.Cell death discovery · 2018Article
- Hypoxic stabilization of mRNA is HIF-independent but requires mtROS.Cellular & molecular biology letters · 2018Article
- Characterization of neural stem cells modified with hypoxia/neuron-specific VEGF expression system for spinal cord injury.Gene therapy · 2018Article
- Article
- Hypoxia and Hypoglycemia synergistically regulate mRNA stability.RNA biology · 2017Article
- Inverse Correlation between IL-10 and HIF-1α in Macrophages Infected with Histoplasma capsulatum.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- The Small Molecule R-(-)-β-O-Methylsynephrine Binds to Nucleoporin 153 kDa and Inhibits Angiogenesis.International journal of biological sciences · 2015Article
- Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity but impaired differentiation with hypoxic preconditioning.Stem cells translational medicine · 2014Article
- Nano-nutrition of chicken embryos. The effect of in ovo administration of diamond nanoparticles and L-glutamine on molecular responses in chicken embryo pectoral muscles.International journal of molecular sciences · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor (VEGF) is a key regulator of developmental, physiological, and tumor angiogenesis. Upregulation of VEGF expression by hypoxia appears to be a critical step in the neovascularization of solid cancers. The VEGF mRNA is intrinsically labile, but in response to hypoxia the mRNA is stabilized. We have systematically analyzed the regions in the VEGF mRNA that are responsible for its lability under normoxic conditions and for stabilization in response to hypoxia. We find that the VEGF mRNA not only contains destabilizing elements in its 3' untranslated region (3'UTR), but also contains destabilizing elements in the 5'UTR and coding region. Each region can independently promote mRNA degradation, and together they act additively to effect rapid degradation under normoxic conditions. Stabilization of the mRNA in response to hypoxia is completely dependent on the cooperation of elements in each of the 5'UTR, coding region, and 3'UTR. Combinations of any of two of these three regions were completely ineffective in responding to hypoxia, whereas combining all three regions allowed recapitulation of the hypoxic stabilization seen with the endogenous VEGF mRNA. We conclude that multiple regions in the VEGF mRNA cooperate both to ensure the rapid degradation of the mRNA under normoxic conditions and to allow stabilization of the mRNA in response to hypoxia. Our findings highlight the complexity of VEGF gene expression and also reveal a mechanism of gene regulation that could become the target for strategies of therapeutic intervention.
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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.