ArticleScientific reports2016
miR-429 regulates the transition between Hypoxia-Inducible Factor (HIF)1A and HIF3A expression in human endothelial cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Changes in the Expression Levels of Hypoxia-Inducible Factor Isoforms and Their Regulating microRNAs in Peripheral Blood Leukocytes after Hypoxic Exposure in Wistar Rats with Different Tolerance to Oxygen Deficiency.Bulletin of experimental biology and medicine · 2026Article
- Article
- Molecular mechanism of the crosstalk between glucocorticoid receptor (GR) and hypoxia-inducible factor 3α (HIF-3α) pathways.Marine life science & technology · 2025Article
- Upregulation ofInternational journal of molecular sciences · 2025Article
- Exploring the therapeutic potential of MOTS-c in age-related macular degeneration: from cellular responses to patient-derived cybrids.Human cell · 2025Article
- Hypoxia inducible factor 3-alpha promotes a malignant phenotype in colorectal cancer cells.IUBMB life · 2025Article
- Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.Current molecular medicine · 2025Review
- Physiological and molecular mechanisms of tolerance to hypoxia and oxygen deficiency resistance markers.Frontiers in molecular biosciences · 2025Review
- PHD2 safeguards modest mesendoderm development.Communications biology · 2024Article
- Hypoxia-inducible factors in postnatal mouse molar dental pulp development: insights into expression patterns, localisation and metabolic pathways.Pflugers Archiv : European journal of physiology · 2024Article
- Exploration of the association between HIF3α mRNA and lncRNA MALAT1 in laryngeal squamous cell carcinoma by correlation analysis.Oncology letters · 2024Article
- Differential expression of miRNAs associated with pectoral myopathies in young broilers: insights from a comparative transcriptome analysis.BMC genomics · 2024Article
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- Methylation of hypoxia-inducible factor 3 subunit alpha contributes to poor prognosis in lung adenocarcinoma.Journal of applied genetics · 2023Article
- HIF-1-Induced hsa-miR-429: Understanding Its Direct Targets as the Key to Developing Cancer Diagnostics and Therapies.Cancers · 2023Review
- Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.bioRxiv : the preprint server for biology · 2023Article
- The Underexplored Landscape of Hypoxia-Inducible Factor 2 Alpha and Potential Roles in Tumor Macrophages: A Review.Oxygen (Basel, Switzerland) · 2023Article
- The Oxygen Cascade from Atmosphere to Mitochondria as a Tool to Understand the (Mal)adaptation to Hypoxia.International journal of molecular sciences · 2023Review
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Authors and funding
9 authors.
Funding
Abstract
Hypoxia-inducible factors (HIF) are heterodimeric transcription factors that allow cells to adapt and survive during hypoxia. Regulation of HIF1A and HIF2A mRNA is well characterized, whereas HIF3A mRNA regulation and function are less clear. Using RNA-Seq analysis of primary human umbilical vein endothelial cells, we found two isoforms of HIF3A were expressed, HIF3A2 and HIF3A3. Comparing HIF3A expression profiles to HIF1A mRNA during 48 hours of hypoxia revealed that HIF1A message peaked at 4 hours, whereas HIF3A expression increased while HIF1A was decreasing. Given that HIF1A mRNA is regulated by miR-429, we tested miR-429 effects on both HIF3A isoforms and found that they too were regulated by miR-429. Analysis of a HIF-3 target, DNA-damage-inducible transcript 4, a key survival gene, indicated that DDIT4 mRNA is induced by HIF-3 and negatively regulated by miR-429 through miR-429's actions on HIF3A message. This provides a compelling model for how hypoxia-induced miR-429 regulates the switch between HIF-1 adaptive responses to HIF-3 survival responses by rapidly decreasing HIF1A levels while simultaneously slowing the progression of HIF3A expression until the miR-429 levels drop below normoxic levels. Since HIF-1 drives HIF3A and miR-429 expression, this establishes a regulatory network in which miR-429 plays a pivotal role.
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