ArticlePLoS genetics2017
Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.Nature genetics · 2024Pooled it
- Association of hypoxia-inducible factor-1α (HIF1α) 1790G/A gene polymorphism with renal cell carcinoma and prostate cancer susceptibility: a meta-analysis.BMC medical genetics · 2019Pooled it
- A network medicine framework for multi-modal data integration in therapeutic target discovery.Communications chemistry · 2026Article
- Generation of a comprehensive epigenomic atlas in clear cell renal cell carcinoma informs kidney cancer progression and heritability.Cell reports · 2026Article
- HIF sustain a transcriptional regulatory circuit of EPAS1 expression in renal clear cell carcinoma.Nature communications · 2026Article
- Unraveling the role of LINC02657 in clear cell renal cell carcinoma: insights into tumor aggression, immune modulation, and treatment response.Frontiers in immunology · 2026Article
- Basic-helix-loop-helix family member e41 suppresses osteoclastogenesis and abnormal bone resorption disease via NFATc1.iScience · 2024Article
- Hypoxia controls expression of kidney-pathogenicLife science alliance · 2023Article
- A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis.Nature communications · 2023Article
- Approach to Functions ofInternational journal of molecular sciences · 2023Review
- Alzheimer's-Associated Upregulation of Mitochondria-Associated ER Membranes After Traumatic Brain Injury.Cellular and molecular neurobiology · 2023Article
- Hypoxia induces polycystin-1 expression in the renal epithelium.Royal Society open science · 2023Article
- Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Article
- Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma.Cancer discovery · 2021Article
- BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma.International journal of molecular sciences · 2021Article
- Functional succinate dehydrogenase deficiency is a common adverse feature of clear cell renal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Altered regulation of DPF3, a member of the SWI/SNF complexes, underlies the 14q24 renal cancer susceptibility locus.American journal of human genetics · 2021Article
- Macrophage migration inhibitory factor is regulated by HIF-1α and cAMP and promotes renal cyst cell proliferation in a macrophage-independent manner.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Signaling in and out: long-noncoding RNAs in tumor hypoxia.Journal of biomedical science · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12.1. This defined a novel stage-specific mechanism in which the risk polymorphism, rs12814794, directly creates a new HIF-binding site that mediates HIF-1α isoform specific upregulation of its target BHLHE41. The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development.
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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.