ArticleOncogene2014
RUNX3 inhibits hypoxia-inducible factor-1α protein stability by interacting with prolyl hydroxylases in gastric cancer cells.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 3 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 3 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Clinicopathological significance and potential drug target of RUNX3 in non-small cell lung cancer: a meta-analysis.Drug design, development and therapy · 2015Pooled it
- Clinicopathological significance of RUNX3 gene hypermethylation in hepatocellular carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Clinicopathological significance and potential drug target of RUNX3 in breast cancer.Drug design, development and therapy · 2014Pooled it
- Foxp1 suppresses cortical angiogenesis and attenuates HIF-1alpha signaling to promote neural progenitor cell maintenance.EMBO reports · 2024Article
- RUNX transcription factors: biological functions and implications in cancer.Clinical and experimental medicine · 2024Review
- Prolyl hydroxylase domain enzyme PHD2 inhibits proliferation and metabolism in non-small cell lung cancer cells in HIF-dependent and HIF-independent manners.Frontiers in oncology · 2024Article
- MicroRNA-495: a therapeutic and diagnostic tumor marker.Journal of molecular histology · 2023Review
- Review
- Review
- Review
- HIF in Gastric Cancer: Regulation and Therapeutic Target.Molecules (Basel, Switzerland) · 2022Review
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis.Translational cancer research · 2022Article
- Review
- Review
- Hypoxia Pathway Proteins and Their Impact on the Blood Vasculature.International journal of molecular sciences · 2021Review
- Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.Cancer discovery · 2018Article
- Emerging role of RUNX3 in the regulation of tumor microenvironment.BMB reports · 2018Review
- Possible Role of PHD Inhibitors as Hypoxia-Mimicking Agents in the Maintenance of Neural Stem Cells' Self-Renewal Properties.Frontiers in cell and developmental biology · 2018Article
- A positive feedback loop promotes HIF-1α stability through miR-210-mediated suppression of RUNX3 in paraquat-induced EMT.Journal of cellular and molecular medicine · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RUNX3 is silenced by histone modification and hypoxia-inducible factor (HIF)-1α is stabilized under hypoxia, but little is known of cross-talk between RUNX3 and HIF-1α under hypoxia. In the present study, the authors investigated the effect of RUNX3 on HIF-1α stability in gastric cancer cells. RUNX3 overexpression was found to downregulate HIF-1α stability under normoxic and hypoxic conditions. Furthermore, the activity of a luciferase reporter containing five copies of vascular endothelial growth factor (VEGF) promoter hypoxia-responsive element (5 × HRE) and the amount of secreted VEGF, were diminished in RUNX3-expressing but increased in RUNX3-knockdown cells. When expression of RUNX3 was recovered using epigenetic reagents the expressions of HIF-1α and VEGF were clearly suppressed under hypoxic conditions. RUNX3 also significantly attenuated the half-life of HIF-1α protein, and induced the cytosolic localization and ubiquitination of HIF-1α. In addition, RUNX3 directly interacted with the C-terminal activation domain of HIF-1α and prolyl hydroxylase (PHD) 2 and enhanced the interaction between HIF-1α and PHD2, which potentiated proline hydroxylation and promoted the degradation of HIF-1α. Furthermore, RUNX3 overexpression significantly inhibited hypoxia-induced angiogenesis in vitro and in vivo. Taken together, these results suggest that RUNX3 destabilizes HIF-1α protein by promoting the proline hydroxylation of HIF-1α through binding to HIF-1α/PHD2. RUNX3 appears to be a novel suppressor of HIF-1α and of hypoxia-mediated angiogenesis in gastric cancer cells.
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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.