ArticleThe Journal of biological chemistry2012
Functional importance of Dicer protein in the adaptive cellular response to hypoxia.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 160 citations in OpenAlex.
- Beyond the Apnea-Hypopnea Index: Circulating Biomarkers and Device-Based Metrics for Cardiometabolic Risk Stratification in Obstructive Sleep Apnea.Journal of clinical medicine · 2026Review
- Adipose Dicer-1 modulates systemic insulin signaling and longevity via a miR-8-Aop-Dilp6 axis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.Current molecular medicine · 2025Review
- Circulating extracellular RNAs, myocardial remodeling, and elevated BMI in patients with acute coronary syndrome.American journal of cardiovascular disease · 2025Article
- Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions.Analytical cellular pathology (Amsterdam) · 2024Review
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- The relationship between prognosis of patients with traumatic brain injury and microRNA biogenesis proteins.Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2023Article
- Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State.Antioxidants (Basel, Switzerland) · 2023Article
- FOXO-mediated repression of Dicer1 regulates metabolism, stress resistance, and longevity inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Breast cancer: miRNAs monitoring chemoresistance and systemic therapy.Frontiers in oncology · 2023Review
- The transition from HIF-1 to HIF-2 during prolonged hypoxia results from reactivation of PHDs and HIF1A mRNA instability.Cellular & molecular biology letters · 2022Article
- MicroRNA-185-5p: a marker of brain-sparing in foetuses with late-onset growth restriction.Epigenetics · 2022Article
- The hypoxia-induced changes in miRNA-mRNA in RNA-induced silencing complexes and HIF-2 induced miRNAs in human endothelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Transcriptional suppression of Dicer by HOXB-AS3/EZH2 complex dictates sorafenib resistance and cancer stemness.Cancer science · 2022Article
- Serum microRNA-185 Levels and Myocardial Injury in Patients with Acute ST-segment Elevation Myocardial Infarction.Internal medicine (Tokyo, Japan) · 2022Article
- Role of MicroRNAs in Extreme Animal Survival Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Epigenetic basis of diabetic vasculopathy.Frontiers in endocrinology · 2022Review
- Article
- Impact of DICER1 and DROSHA on the Angiogenic Capacity of Human Endothelial Cells.International journal of molecular sciences · 2021Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The processes by which cells sense and respond to ambient oxygen concentration are fundamental to cell survival and function, and they commonly target gene regulatory events. To date, however, little is known about the link between the microRNA pathway and hypoxia signaling. Here, we show in vitro and in vivo that chronic hypoxia impairs Dicer (DICER1) expression and activity, resulting in global consequences on microRNA biogenesis. We show that von Hippel-Lindau-dependent down-regulation of Dicer is key to the expression and function of hypoxia-inducible factor α (HIF-α) subunits. Specifically, we show that EPAS1/HIF-2α is regulated by the Dicer-dependent microRNA miR-185, which is down-regulated by hypoxia. Full expression of hypoxia-responsive/HIF target genes in chronic hypoxia (e.g. VEGFA, FLT1/VEGFR1, KDR/VEGFR2, BNIP3L, and SLC2A1/GLUT1), the function of which is to regulate various adaptive responses to compromised oxygen availability, is also dependent on hypoxia-mediated down-regulation of Dicer function and changes in post-transcriptional gene regulation. Therefore, functional deficiency of Dicer in chronic hypoxia is relevant to both HIF-α isoforms and hypoxia-responsive/HIF target genes, especially in the vascular endothelium. These findings have relevance to emerging therapies given that we show that the efficacy of RNA interference under chronic hypoxia, but not normal oxygen availability, is Dicer-dependent. Collectively, these findings show that the down-regulation of Dicer under chronic hypoxia is an adaptive mechanism that serves to maintain the cellular hypoxic response through HIF-α- and microRNA-dependent mechanisms, thereby providing an essential mechanistic insight into the oxygen-dependent microRNA regulatory pathway.
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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.