ArticleMolecular and cellular biology2011
MDM2 regulates vascular endothelial growth factor mRNA stabilization in hypoxia.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 88 citations in OpenAlex.
- A diabetes-induced change of MDM2 SNP309T→G contributes to aberrant retinal angiogenesis.Diabetologia · 2026Article
- The MDM2 SNP309 differentially impacts cardiorespiratory fitness in young healthy women and men.European journal of applied physiology · 2025Article
- Association of Insertion/Deletion Polymorphisms of MDM2, MCP-1 and VEGF with Esophageal Cancer Risk in North-West Indians: A Case - Control Study.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Evaluation of the antiangiogenic effect of AMG232 in multiple myeloma coculture systems.Medical oncology (Northwood, London, England) · 2025Article
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges.Biomedicines · 2025Review
- MDM2 interacts with PTEN to inhibit endothelial cell development and promote deep vein thrombosis via the JAK/STAT signaling pathway.Molecular medicine reports · 2025Article
- MDM2 inhibitors in cancer immunotherapy: Current status and perspective.Genes & diseases · 2024Review
- 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
- The role of MDM2 in angiogenesis: implications for endothelial tip cell formation.In vitro cellular & developmental biology. Animal · 2024Article
- Article
- MicroRNAs and angiosarcoma: are there promising reports?Frontiers in oncology · 2024Review
- MDM2 amplification is rare in gastric cancer.Virchows Archiv : an international journal of pathology · 2023Article
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Synthesis and biological evaluation of dual MDM2/XIAP inhibitors based on the tetrahydroquinoline scaffold.European journal of medicinal chemistry · 2023Article
- Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma.BMC cancer · 2023Article
- Article
- MYCN mRNA degradation and cancer suppression by a selective small-molecule inhibitor in MYCN-amplified neuroblastoma.Frontiers in oncology · 2022Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- ZEB2, interacting with MDM2, contributes to the dysfuntion of brain microvascular endothelial cells and brain injury after intracerebral hemorrhage.Cell cycle (Georgetown, Tex.) · 2021Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Expression of vascular endothelial growth factor (VEGF) increases in cancer cells during hypoxia. Herein, we report that the MDM2 oncoprotein plays a role in hypoxia-mediated VEGF upregulation. In studying the characteristics of MDM2 and VEGF expression in neuroblastoma cells, we found that hypoxia induced significantly higher upregulation of both VEGF mRNA and protein in MDM2-positive cells than in the MDM2-negative cells, even in cells without wild-type (wt) p53. We found that hypoxia induced translocation of MDM2 from the nucleus to the cytoplasm, which was associated with increased VEGF expression. Enforcing overexpression of cytoplasmic MDM2 by transfection of the mutant MDM2/166A enhanced expression of VEGF mRNA and protein production, even without hypoxia. The results of mechanistic studies demonstrated that the C-terminal RING domain of the MDM2 protein bound to the AU-rich sequence within the 3' untranslated region (3'UTR) of VEGF mRNA; this binding increased VEGF mRNA stability and translation. In addition, knockdown of MDM2 by small interfering RNA (siRNA) in MDM2-overexpressing cancer cells resulted in inhibition of VEGF protein production, cancer cell survival, and angiogenesis. Our results suggest that MDM2 plays a p53-independent role in the regulation of VEGF, which may promote tumor growth and metastasis.
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Registered trials
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.