ArticleCellular oncology (Dordrecht, Netherlands)2014
Transcription of the vascular endothelial growth factor receptor-3 (VEGFR3) gene is regulated by the zinc finger proteins Sp1 and Sp3 and is under epigenetic control: transcription of vascular endothelial growth factor receptor 3.
Article in Cellular oncology (Dordrecht, Netherlands), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development.Current issues in molecular biology · 2023Review
- A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner.Angiogenesis · 2021Article
- Correlation amongTranslational cancer research · 2020Article
- High Glucose Induces Endothelial COX2 and iNOS Expression via Inhibition of Monomethyltransferase SETD8 Expression.Journal of diabetes research · 2020Article
- Sp1 Suppresses miR-3178 to Promote the Metastasis Invasion Cascade via Upregulation of TRIOBP.Molecular therapy. Nucleic acids · 2018Article
- Targeting VEGF/VEGFRs Pathway in the Antiangiogenic Treatment of Human Cancers by Traditional Chinese Medicine.Integrative cancer therapies · 2018Review
- Recent advances in understanding lymphangiogenesis and metabolism.F1000Research · 2018Review
- Trefoil factor family 2 expression inhibits gastric cancer cell growth and invasion in vitro via interactions with the transcription factor Sp3.International journal of molecular medicine · 2016Article
- IGF-1 signaling in neonatal hypoxia-induced pulmonary hypertension: Role of epigenetic regulation.Vascular pharmacology · 2015Article
- Article
- Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats.BMC genomics · 2014Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn the past, the vascular endothelial growth factor receptor-3 (VEGFR-3) has been linked to the regulation of lymphangiogenesis and the lymphatic spread of solid malignancies. The molecular mechanisms controlling VEGFR3 gene expression have, however, remained poorly understood. Here, we aimed at assessing these mechanisms through VEGFR3 gene promoter analysis and the identification of transcription factors binding to it. In addition, we focussed on epigenetic modifications underlying VEGFR3 transcription regulation.
methods5' Deletion analyses for the identification of functional promoter elements, electrophoretic mobility shift assays, chromatin immunoprecipitations, methylation-specific PCRs, and Trichostatin A (TSA) and 5-Aza desoxycytidine (5-Aza dC) treatments were performed in this study.
resultsFollowing the isolation of a 2 kb stretch of 5'-flanking DNA of VEGFR3, we identified a novel GC-rich element (GRE) spanning -101/-66 sufficient for VEGFR3 transcription and activated by Sp1 and Sp3, respectively. Histone de-acetylase inhibition by TSA led to the accumulation of acetylated histones H3/H4 at the VEGFR3 gene promoter, up-regulation of its mRNA levels, and transactivation of promoter reporter constructs in endothelial cell lines. Similarly, methylation inhibition by 5-Aza dC triggered up-regulation of VEGFR3 mRNA levels and increased promoter activity. TSA and 5-Aza-dC did not influence Sp1/Sp3 binding, but increased the transactivating capacity of both transcription factors, suggesting epigenetic modification as an underlying mechanism.
conclusionsHere we describe the identification of regulatory elements controlling human VEGFR3 gene expression and show that histone acetylation and CpG methylation are important determinants of VEGFR3 transcription regulation. These findings may facilitate the development of intervention strategies aimed at targeting VEGFR3-based tumor lymphangiogenesis and/or lymphatic tumor spread.
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