ArticleCell communication and signaling : CCS2019
ΗΙF1α, EGR1 and SP1 co-regulate the erythropoietin receptor expression under hypoxia: an essential role in the growth of non-small cell lung cancer cells.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 29 citations in OpenAlex.
- Elucidating the Molecular Network Underpinning Hypoxia Adaptation in the Liver of Silver Carp (Animals : an open access journal from MDPI · 2025Article
- Article
- Interaction and Collaboration of SP1, HIF-1, and MYC in Regulating the Expression of Cancer-Related Genes to Further Enhance Anticancer Drug Development.Current issues in molecular biology · 2023Review
- A systematic study of HIF1A cofactors in hypoxic cancer cells.Scientific reports · 2022Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- METTL7B contributes to the malignant progression of glioblastoma by inhibiting EGR1 expression.Metabolic brain disease · 2022Article
- Using biological information to analyze potential miRNA-mRNA regulatory networks in the plasma of patients with non-small cell lung cancer.BMC cancer · 2022Article
- MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA.Bioengineered · 2022Article
- Pan-Cancer Analysis Based onFrontiers in oncology · 2022Article
- Integrated bioinformatical analysis, machine learning andFrontiers in pharmacology · 2022Article
- Serine 26 in Early Growth Response-1 Is Critical for Endothelial Proliferation, Migration, and Network Formation.Journal of the American Heart Association · 2021Article
- Subnormothermic Perfusion with HBiomolecules · 2021Article
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- The Role of Early Growth Response Family Members 1-4 in Prognostic Value of Breast Cancer.Frontiers in genetics · 2021Article
- Hypoxia-Inducible Factor Regulates Endothelial Metabolism in Cardiovascular Disease.Frontiers in physiology · 2021Review
- Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis.International journal of molecular sciences · 2020Review
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8 authors at 5 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundOverexpression of erythropoietin (EPO) and EPO receptor (EPO-R) is associated with poor prognosis in non-small-cell lung carcinoma (NSCLC). Hypoxia, a potent EPO inducer, is a major stimulating factor in the growth of solid tumors. However, how EPO-R expression is regulated under hypoxia is largely unknown.
methodsThe role of EPO-R in NSCLC cell proliferation was assessed by RNA interference in vitro. Luciferase reporter assays were performed to map the promoter elements involved in the EPO-R mRNA transcription. Nuclear co-immunoprecipitation and chromatin immunoprecipitation were performed to assess the interaction among transcription factors HIF1α, SP1, and EGR1 in the regulation of EPO-R under hypoxia. The expression of key EPO-R transcription factors in clinical specimens were determined by immunohistochemistry.
resultsHypoxia induced a dosage and time dependent EPO-R mRNA expression in NSCLC cells. Knockdown of EPO-R reduced NSCLC cell growth under hypoxia (P < 0.05). Mechanistically, a SP1-EGR1 overlapped DNA binding sequence was essential to the hypoxia induced EPO-R transcription. In the early phase of hypoxia, HIF1α interacted with EGR1 that negatively regulated EPO-R. With the exit of EGR1 in late phase, HIF1α positively regulated EPO-R expression through additive interaction with SP1. In clinical NSCLC specimen, SP1 was positively while EGR1 was negatively associated with active EPO-R expression (P < 0.05).
conclusionsHIF1α, SP1 and EGR1 mediated EPO-R expression played an essential role in hypoxia-induced NSCLC cell proliferation. Our study presents a novel mechanism of EPO-R regulation in the tumor cells, which may provide information support for NSCLC diagnosis and treatment.
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