LET-Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of miRNAs that Drive Inhibition

Autor: Yen-Ruh Wuu, Burong Hu, Hazeem Okunola, Amber M. Paul, Elizabeth A. Blaber, Margareth Cheng-Campbell, Afshin Beheshti, Peter Grabham
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: iScience, Vol 23, Iss 12, Pp 101771- (2020)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2020.101771
Popis: Summary: Space 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 (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.
Databáze: Directory of Open Access Journals