ArticleBlood2014
Hydroxyurea-inducible SAR1 gene acts through the Giα/JNK/Jun pathway to regulate γ-globin expression.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease.Expert review of hematology · 2015Pooled it
- Differential MicroRNA Profiles Associated With the Hydroxyurea-InducibleJournal of hematology · 2025Article
- Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models.Frontiers in pharmacology · 2025Article
- Hydroxyurea inhibits proliferation and stimulates apoptosis through inducible nitric oxide synthase in erythroid cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- SAR1A Induces Cell Growth and Epithelial-Mesenchymal Transition Through the PI3K/AKT/mTOR Pathway in Head and Neck Squamous Cell Carcinoma: An In Vitro and In Vivo Study.Biomedicines · 2024Article
- Article
- Single nucleotide polymorphisms inEJHaem · 2022Article
- Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Molecular Determination of Vascular Endothelial Growth Factor, miRNA-423 Gene Abnormalities by Utilizing ARMS-PCR and Their Association with Fetal Hemoglobin Expression in the Patients with Sickle Cell Disease.Current issues in molecular biology · 2022Article
- Transmembrane Protein ANTXR1 RegulatesJournal of immunology research · 2022Article
- Erythrocyte microRNAs: a tiny magic bullet with great potential for sickle cell disease therapy.Annals of hematology · 2021Review
- A comprehensive review of hydroxyurea for β-haemoglobinopathies: the role revisited during COVID-19 pandemic.Orphanet journal of rare diseases · 2021Review
- Characterization of natural killer cells expressing markers associated with maturity and cytotoxicity in children and young adults with sickle cell disease.Pediatric blood & cancer · 2019Article
- Hydroxyurea-Induced miRNA Expression in Sickle Cell Disease Patients in Africa.Frontiers in genetics · 2019Article
- Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis.Scientific reports · 2017Article
- SAR1a promoter polymorphisms are not associated with fetal hemoglobin in patients with sickle cell disease from Cameroon.BMC research notes · 2017Article
- Cellular therapy for sickle cell disease.Cytotherapy · 2016Review
- An Expert Review of Pharmacogenomics of Sickle Cell Disease Therapeutics: Not Yet Ready for Global Precision Medicine.Omics : a journal of integrative biology · 2016Review
- Article
- Hydroxyurea down-regulates BCL11A, KLF-1 and MYB through miRNA-mediated actions to induce γ-globin expression: implications for new therapeutic approaches of sickle cell disease.Clinical and translational medicine · 2016Article
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6 authors at 2 institutions in 1 country.
Funding
Abstract
Hydroxyurea (HU) is effectively used in the management of β-hemoglobinopathies by augmenting the production of fetal hemoglobin (HbF). However, the molecular mechanisms underlying HU-mediated HbF regulation remain unclear. We previously reported that overexpression of the HU-induced SAR1 gene closely mimics the known effects of HU on K562 and CD34(+) cells, including γ-globin induction and cell-cycle regulation. Here, we show that HU stimulated nuclear factor-κB interaction with its cognate-binding site on the SAR1 promoter to regulate transcriptional expression of SAR1 in K562 and CD34(+) cells. Silencing SAR1 expression not only significantly lowered both basal and HU-elicited HbF production in K562 and CD34(+) cells, but also significantly reduced HU-mediated S-phase cell-cycle arrest and apoptosis in K562 cells. Inhibition of c-Jun N-terminal kinase (JNK)/Jun phosphorylation and silencing of Giα expression in SAR1-transfected K562 and CD34(+) cells reduced both γ-globin expression and HbF level, indicating that activation of Giα/JNK/Jun proteins is required for SAR1-mediated HbF induction. Furthermore, reciprocal coimmunoprecipitation assays revealed an association between forcibly expressed SAR1 and Giα2 or Giα3 proteins in both K562 and nonerythroid cells. These results indicate that HU induces SAR1, which in turn activates γ-globin expression, predominantly through the Giα/JNK/Jun pathway. Our findings identify SAR1 as an alternative therapeutic target for β-globin disorders.
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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 Socratic graph.