ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022
The hypoxia-induced changes in miRNA-mRNA in RNA-induced silencing complexes and HIF-2 induced miRNAs in human endothelial cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Downregulation of circ_0001112 Enhances Myocardial Infarction Through Regulation of miR-324-5p/CDK6 Axis.Journal of biochemical and molecular toxicology · 2026Article
- Predictive Value of PreoperativeInternational journal of molecular sciences · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- Colon Histophysiological Features and Gut Microbiome in Tolerant and Susceptible to Oxygen Deficiency Wistar Rats After the Prolonged Intermittent Hypoxic Exposure.Biomolecules · 2026Article
- Skeletal Muscle miRNA Patterns in High-Altitude Trekkers: Exploratory Identification of Molecular Signatures of Cellular and Endocrine Adaptation.Biomolecules · 2026Article
- miRNA675-5p inhibitor's dual role as novel therapeutic alternative or sensitizing treatment in resistant glioma models.Molecular therapy. Nucleic acids · 2026Article
- 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
- Targeting shared mechanisms of cisplatin resistance and metastasis in lung cancer for novel therapeutic strategies.Discover oncology · 2026Review
- MicroRNAs and genes regulating responses to hypoxia and inflammation expression levels in blood leukocytes as potential biomarkers of initial oxygen deficiency tolerance.Frontiers in molecular biosciences · 2026Article
- Challenges in mimicking hypoxia: insights into HIF-regulated MiRNA expression induced by DMOG and CoClCell communication and signaling : CCS · 2025Article
- Old drugs, new challenges: reassigning drugs for cancer therapies.Cellular & molecular biology letters · 2025Review
- Gene expression and DNA methylation changes in response to hypoxia in toxicant-adapted Atlantic killifish (Fundulus heteroclitus).Biology open · 2025Article
- A dynamic model of gene activation in response to hypoxia accounting for both HIF-1 and HIF-2.Briefings in functional genomics · 2025Article
- miR-1233-3p Inhibits Angiopoietin-1-Induced Endothelial Cell Survival, Migration, and Differentiation.Cells · 2025Article
- HIF-2α accumulation in human monocytes upon transfer of hypoxia-associated miRNAs via plasma-derived small extracellular vesicles from head and neck cancer patients.Frontiers in oncology · 2025Article
- Physiological and molecular mechanisms of tolerance to hypoxia and oxygen deficiency resistance markers.Frontiers in molecular biosciences · 2025Review
- Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.International journal of molecular sciences · 2024Review
- Intertwined regulators: hypoxia pathway proteins, microRNAs, and phosphodiesterases in the control of steroidogenesis.Pflugers Archiv : European journal of physiology · 2024Review
- The Untapped Biomarker Potential of MicroRNAs for Health Risk-Benefit Analysis of Vaping vs. Smoking.Cells · 2024Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The cellular adaptive response to hypoxia relies on the expression of hypoxia-inducible factors (HIFs), HIF-1 and HIF-2. HIFs regulate global gene expression changes during hypoxia that are necessary for restoring oxygen homeostasis and promoting cell survival. In the early stages of hypoxia, HIF-1 is elevated, whereas at the later stages, HIF-2 becomes the predominant form. What governs the transition between the two HIFs (the HIF switch) and the role of miRNAs in this regulation are not completely clear. Genome-wide expression studies on the miRNA content of RNA-induced silencing complexes (RISC) in HUVECs exposed to hypoxia compared to the global miRNA-Seq analysis revealed very specific differences between these two populations. We analyzed the miRNA and mRNA composition of RISC at 2 h (mainly HIF-1 driven), 8 h (HIF-1 and HIF-2 elevated), and 16 h (mainly HIF-2 driven) in a gene ontology context. This allowed for determining the direct impact of the miRNAs in modulating the cellular signaling pathways involved in the hypoxic adaptive response. Our results indicate that the miRNA-mRNA RISC components control the adaptive responses, and this does not always rely on the miRNA transcriptional elevations during hypoxia. Furthermore, we demonstrate that the hypoxic levels of the vast majority of HIF-1-dependent miRNAs (including miR-210-3p) are also HIF-2 dependent and that HIF-2 governs the expression of 11 specific miRNAs. In summary, the switch from HIF-1 to HIF-2 during hypoxia provides an important level of miRNA-driven control in the adaptive pathways in endothelial cells.
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Registered trials
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