ArticleThe Journal of biological chemistry2013
Identification of DEAD-box RNA helicase 6 (DDX6) as a cellular modulator of vascular endothelial growth factor expression under hypoxia.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways.Nature communications · 2019Pooled it
- Reshaping cancer cell plasticity by P-body dynamics and protein translation.Communications biology · 2026Review
- DEAD-box helicase family proteins: emerging targets in digestive system cancers and advances in targeted drug development.Journal of translational medicine · 2024Review
- Non-coding RNAs and angiogenesis in cardiovascular diseases: a comprehensive review.Molecular and cellular biochemistry · 2024Review
- DEAD-box RNA helicases in the multistep process of tumor metastasis.Molecular biology reports · 2024Review
- Unraveling the Etiology of Dilated Cardiomyopathy through Differential miRNA-mRNA Interactome.Biomolecules · 2024Article
- miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells.Blood advances · 2023Article
- Plumbagin Suppresses Breast Cancer Progression by Downregulating HIF-1α Expression via a PI3K/Akt/mTOR Independent Pathway under Hypoxic Condition.Molecules (Basel, Switzerland) · 2022Article
- The Immunogenetics of Systemic Sclerosis.Advances in experimental medicine and biology · 2022Article
- The Pathophysiological Roles of Regulatory T Cells in the Early Phase of Systemic Sclerosis.Frontiers in immunology · 2022Review
- Altered Cellular Immunity and Differentially Expressed Immune-Related Genes in Patients With Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.Frontiers in immunology · 2022Article
- miR-152-3p aggravates vascular endothelial cell dysfunction by targeting DEAD-box helicase 6 (DDX6) under hypoxia.Bioengineered · 2021Article
- Translational control in neurovascular brain development.Royal Society open science · 2021Review
- Specific Interaction of DDX6 with an RNA Hairpin in the 3' UTR of the Dengue Virus Genome Mediates GJournal of virology · 2021Article
- Methylated HNRNPK acts on RPS19 to regulate ALOX15 synthesis in erythropoiesis.Nucleic acids research · 2021Article
- RNA Helicases as Shadow Modulators of Cell Cycle Progression.International journal of molecular sciences · 2021Review
- miR-130a activates the VEGFR2/STAT3/HIF1α axis to potentiate the vasoregenerative capacity of endothelial colony-forming cells in hypoxia.Molecular therapy. Nucleic acids · 2021Article
- P23 Acts as Functional RBP in the Macrophage Inflammation Response.Frontiers in molecular biosciences · 2021Article
- General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation.International journal of molecular sciences · 2020Review
- On the optimal design of metabolic RNA labeling experiments.PLoS computational biology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor A (VEGF) is a crucial proangiogenic factor, which regulates blood vessel supply under physiologic and pathologic conditions. The VEGF mRNA 5'-untranslated region (5'-UTR) bears internal ribosome entry sites (IRES), which confer sustained VEGF mRNA translation under hypoxia when 5'-cap-dependent mRNA translation is inhibited. VEGF IRES-mediated initiation of translation requires the modulated interaction of trans-acting factors. To identify trans-acting factors that control VEGF mRNA translation under hypoxic conditions we established an in vitro translation system based on human adenocarcinoma cells (MCF-7). Cytoplasmic extracts of MCF-7 cells grown under hypoxia (1% oxygen) recapitulate VEGF IRES-mediated reporter mRNA translation. Employing the VEGF mRNA 5'-UTR and 3'-UTR in an RNA affinity approach we isolated interacting proteins from translational active MCF-7 extract prepared from cells grown under normoxia or hypoxia. Interestingly, mass spectrometry analysis identified the DEAD-box RNA helicase 6 (DDX6) that interacts with the VEGF mRNA 5'-UTR. Recombinant DDX6 inhibits VEGF IRES-mediated translation in normoxic MCF-7 extract. Under hypoxia the level of DDX6 declines, and its interaction with VEGF mRNA is diminished in vivo. Depletion of DDX6 by RNAi further promotes VEGF expression in MCF-7 cells. Increased secretion of VEGF from DDX6 knockdown cells positively affects vascular tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Our results indicate that the decrease of DDX6 under hypoxia contributes to the activation of VEGF expression and promotes its proangiogenic function.
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