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标题：LET-Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of miRNAs that Drive Inhibition
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作者：Yen-Ruh Wuu ; Burong Hu ; Hazeem Okunola 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：12
页码：1-28
DOI：10.1016/j.isci.2020.101771
语种：English
出版社：Elsevier
摘要：SummarySpace radiation inhibits angiogenesis by two mechanisms depending on the linear energy transfer (LET). Using human 3D micro-vessel models, blockage of the early motile stage of angiogenesis was determined to occur after exposure to low LET ions (<3 KeV/AMU), whereas inhibition of the later stages occurs after exposure to high LET ions (>8 KeV/AMU). Strikingly, the combined effect is synergistic, detectible as low as 0.06 Gy making mixed ion space radiation more potent. Candidates for bystander transmission are microRNAs (miRNAs), and analysis on miRNA-seq data from irradiated mice shows that angiogenesis would in theory be downregulated. Further analysis of three previously identified miRNAs showed downregulation of their targets associated with angiogenesis and confirmed their involvement in angiogenesis pathways and increased health risks associated with cardiovascular disease. Finally, synthetic molecules (antagomirs) designed to inhibit the predicted miRNAs were successfully used to reverse the inhibition of angiogenesis.Graphical AbstractDisplay OmittedHighlights•Space radiation inhibits angiogenesis synergistically at low doses by 2 mechanisms•Candidates for bystander transmission are microRNAs•Three previously identified miRNAs showed downregulation of their angiogenesis targets•Synthetic miRNA inhibitors were used to reverse the inhibition of angiogenesisRadiation Biology; Molecular Biology; Space Sciences