ArticleProceedings of the National Academy of Sciences of the United States of America2011
MicroRNA let-7 establishes expression of beta2-adrenergic receptors and dynamically down-regulates agonist-promoted down-regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. 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, 42 citations in OpenAlex.
- Beneath the surface: endosomal GPCR signaling.Trends in biochemical sciences · 2024Review
- Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction.Minerva medica · 2022Article
- The role of ADRB2 gene polymorphisms in malignancies.Molecular biology reports · 2021Review
- Regulation of βNeural regeneration research · 2020Review
- Differential long-term regulation of TAS2R14 by structurally distinct agonists.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases?Archivum immunologiae et therapiae experimentalis · 2019Review
- HER2 in stemness and epithelial-mesenchymal plasticity of breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Single nucleotide polymorphisms of let-7-related genes increase susceptibility to breast cancer.American journal of translational research · 2019Article
- hsa-miR-3177-5p and hsa-miR-3178 Inhibit 5-HT1A Expression by Binding the 3'-UTR RegionFrontiers in molecular neuroscience · 2019Article
- A CREB-mediated increase in miRNA let-7f during prolonged β-agonist exposure: a novel mechanism of βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- A single-nucleotide polymorphism of the beta 2-adrenergic receptor gene can predict pathological complete response to taxane- and platinum-based neoadjuvant chemotherapy in breast cancer.Breast cancer (Dove Medical Press) · 2018Article
- MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential.Current heart failure reports · 2017Review
- Regulation of Pharmacogene Expression by microRNA in The Cancer Genome Atlas (TCGA) Research Network.Biomolecules & therapeutics · 2017Article
- Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells.Scientific reports · 2016Article
- A Her2-let-7-β2-AR circuit affects prognosis in patients with Her2-positive breast cancer.BMC cancer · 2015Article
- MicroRNA circulating in the early aftermath of motor vehicle collision predict persistent pain development and suggest a role for microRNA in sex-specific pain differences.Molecular pain · 2015Article
- Effects of Rosmarinus officinalis extract on human primary omental preadipocytes and adipocytes.Experimental biology and medicine (Maywood, N.J.) · 2015Article
- CD38 and airway hyper-responsiveness: studies on human airway smooth muscle cells and mouse models.Canadian journal of physiology and pharmacology · 2015Review
- Identification and Functional Characterization of Cis-Regulatory Elements Controlling Expression of the Porcine ADRB2 Gene.International journal of biological sciences · 2015Article
- MicroRNA-708 regulates CD38 expression through signaling pathways JNK MAP kinase and PTEN/AKT in human airway smooth muscle cells.Respiratory research · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Although β(2)-adrenergic receptors (β(2)AR) are expressed on most cell types, mechanisms that establish expression levels and regulate expression by chronic agonist remain unclear. The 3' UTR of ADRB2 has a conserved 8-nucleotide seed region that we hypothesized is targeted by the let-7 family of miRNAs leading to translational repression. In luciferase assays with transfected cells, luc-β(2)WT3'UTR had decreased expression when cotransfected with let-7f, but a mutated luc-β(2)3'UTR lacking the seed was unaffected by let-7f; a mutated let-7f also had no effect on luc-β(2)WT3'UTR expression. ADRB2 mRNA was in greater abundance in immunoprecipitates of Ago2, a core component of the miRNA-induced silencing complex, when cells were transfected with let-7f, but not with a mutated let-7f, indicating a direct interaction with the silencing mechanism. H292 cells transfected with let-7f caused ∼60% decrease in native β(2)AR expression, but transfection with let-7f-specific locked nucleic acid anti-miRNA increased β(2)AR expression by ∼twofold. We considered that an increase in let-7f leading to greater repression of translation contributes to agonist-promoted down-regulation. Paradoxically, in cells and in lungs from mice treated in vivo, an ∼50% decrease in let-7f occurs during long-term agonist exposure, indicating a counterregulatory event. Consistent with this notion, let-7f locked nucleic acid transfection caused depressed agonist-promoted down-regulation. Thus, let-7f miRNA regulates baseline β(2)AR expression and decreases in let-7f evoked by agonist attenuate down-regulation. This positive feedback loop has not previously been described for a G protein-coupled receptor and its miRNA. Methods to decrease let-7f expression in targeted cells may increase therapeutic responses to β-agonist by increasing β(2)AR expression or minimizing tachyphylaxis.
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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.