ArticleScientific reports2018
Consequences of VHL Loss on Global DNA Methylome.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- DNA methyltransferase inhibition is a therapeutic vulnerability in VHL-deficient renal cell carcinoma cells.Experimental & molecular medicine · 2026Article
- Von Hippel-Lindau/Hypoxia Inducible Factor Axis in Glioblastoma.International journal of molecular sciences · 2025Review
- Hypoxia-induced genome-wide DNA demethylation by DNMT3A and EMT of cancer cells.Cellular & molecular biology letters · 2025Article
- Advancing the Landscape of Clinical Actionability in Von Hippel-Lindau Syndrome: An Evidence-Based Framework from the INTCancers · 2025Article
- Preliminary Study of Whole-Genome Bisulfite Sequencing and Transcriptome Sequencing in VHL Disease-Associated ccRCC.Molecular diagnosis & therapy · 2023Article
- Article
- Hypoxia-inducible factor-1β is essential for upregulation of the hypoxia-induced FLT1 gene in placental trophoblasts.Molecular human reproduction · 2021Article
- Review
- Epigenetics modifiers: potential hub for understanding and treating neurodevelopmental disorders from hypoxic injury.Journal of neurodevelopmental disorders · 2020Review
- TET is targeted for proteasomal degradation by the PHD-pVHL pathway to reduce DNA hydroxymethylation.The Journal of biological chemistry · 2020Article
- VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3β signaling.Journal of experimental & clinical cancer research : CR · 2020Article
- Article
- Production of an anti-angiogenic factor sFLT1 is suppressed via promoter hypermethylation of FLT1 gene in choriocarcinoma cells.BMC cancer · 2020Article
- Uptake of HDL-cholesterol contributes to lipid accumulation in clear cell renal cell carcinoma.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia.Nature communications · 2019Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
In clear-cell renal cell carcinoma (ccRCC), loss of von Hippel-Lindau (VHL) tumour suppressor gene and reduced oxygen tension promote stabilisation of hypoxia-inducible factor (HIF) family of transcription factors, which promote changes in the expression of genes that contribute to oncogenesis. Multiple studies have demonstrated significant perturbations in DNA methylation in ccRCC via largely unclear mechanisms that modify the transcriptional output of tumour cells. Here, we show that the methylation status of the CpG dinucleotide within the consensus hypoxia-responsive element (HRE) markedly influences the binding of HIF and that the loss of VHL results in significant alterations in the DNA methylome. Surprisingly, hypoxia, which likewise promotes HIF stabilisation and activation, has relatively few effects on global DNA methylation. Gene expression analysis of ccRCC patient samples highlighted expression of a group of genes whose transcription correlated with methylation changes, including hypoxic responsive genes such as VEGF and TGF. These results suggest that the loss of VHL alters DNA methylation profile across the genome, commonly associated with and contributing to ccRCC progression.
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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.