LET-Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of miRNAs that Drive Inhibition.
Molecular Biology
Radiation Biology
Space Sciences
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
18 Dec 2020
18 Dec 2020
Historique:
received:
18
07
2020
revised:
19
10
2020
accepted:
31
10
2020
entrez:
30
12
2020
pubmed:
31
12
2020
medline:
31
12
2020
Statut:
epublish
Résumé
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 (<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.
Identifiants
pubmed: 33376971
doi: 10.1016/j.isci.2020.101771
pii: S2589-0042(20)30968-8
pmc: PMC7756138
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101771Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
Curr Genomics. 2010 Nov;11(7):537-61
pubmed: 21532838
Radiat Res. 2011 Jun;175(6):766-73
pubmed: 21466380
Life Sci Space Res (Amst). 2017 May;13:1-11
pubmed: 28554504
Radiat Res. 2018 Jul;190(1):45-52
pubmed: 29741442
Int J Mol Sci. 2019 Nov 30;20(23):
pubmed: 31801298
Cancer Treat Rev. 2017 Feb;53:120-127
pubmed: 28104567
PLoS One. 2015 Mar 12;10(3):e0119646
pubmed: 25763857
Nat Rev Cardiol. 2018 Mar;15(3):167-180
pubmed: 29053152
Life Sci Space Res (Amst). 2016 Aug;10:53-6
pubmed: 27662788
PLoS One. 2009 Jul 27;4(7):e6377
pubmed: 19633716
Aviat Space Environ Med. 2009 Feb;80(2):117-24
pubmed: 19198198
PLoS One. 2018 Jul 25;13(7):e0199621
pubmed: 30044882
Eur Heart J. 2010 Mar;31(6):649-58
pubmed: 20118173
Int J Radiat Biol. 2011 Sep;87(9):954-63
pubmed: 21732726
Vasc Cell. 2013 Sep 17;5(1):16
pubmed: 24044765
PLoS One. 2010 Jun 21;5(6):e11222
pubmed: 20574535
Int J Radiat Biol. 2012 Jul;88(7):531-9
pubmed: 22551419
Cancer Res. 2009 Mar 15;69(6):2296-304
pubmed: 19258501
Vasc Cell. 2013 Oct 26;5(1):19
pubmed: 24160185
Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):131-138
pubmed: 26725728
J Neurooncol. 2000 Oct-Nov;50(1-2):139-48
pubmed: 11245273
Cells. 2018 Dec 06;7(12):
pubmed: 30563269
Nature. 2005 Dec 1;438(7068):685-9
pubmed: 16258535
Radiat Res. 2010 Apr;173(4):486-93
pubmed: 20334521
PLoS One. 2015 Sep 22;10(9):e0138383
pubmed: 26394310
Cells. 2019 Jul 18;8(7):
pubmed: 31323768
World J Cardiol. 2015 Dec 26;7(12):882-8
pubmed: 26730293
Int J Dev Biol. 2011;55(4-5):353-63
pubmed: 21732275
Cancer Res. 2001 Mar 15;61(6):2744-50
pubmed: 11289157
Int J Radiat Oncol Biol Phys. 2010 Aug 1;77(5):1518-26
pubmed: 19906497
Hypertension. 2018 Apr;71(4):638-647
pubmed: 29483228
N Engl J Med. 2016 Oct 13;375(15):1457-1467
pubmed: 27732808
PLoS Biol. 2020 May 19;18(5):e3000669
pubmed: 32428004
Int J Radiat Biol. 2012 Jun;88(6):493-500
pubmed: 22449005
Eur J Prev Cardiol. 2019 Nov;26(16):1707-1714
pubmed: 30776915
Organogenesis. 2010 Jan-Mar;6(1):1-10
pubmed: 20592859
Radiat Res. 2011 Oct;176(4):474-85
pubmed: 21787183
Radiat Res. 2012 Jul;178(1):33-45
pubmed: 22702646
Microvasc Res. 2013 Mar;86:11-20
pubmed: 23220351
Int J Radiat Biol. 1999 Feb;75(2):201-8
pubmed: 10072181
Sci Rep. 2016 Jul 28;6:29901
pubmed: 27467019
Radiat Res. 2013 Mar;179(3):257-72
pubmed: 23373900
FASEB J. 2015 Dec;29(12):4893-900
pubmed: 26276131
Sci Rep. 2019 Nov 20;9(1):17161
pubmed: 31748664
Front Pharmacol. 2017 Sep 22;8:570
pubmed: 28993729
FASEB J. 2016 Jun;30(6):2211-24
pubmed: 26917741
Radiat Res. 2011 Jan;175(1):21-8
pubmed: 21175343
Autoimmun Rev. 2016 Dec;15(12):1171-1180
pubmed: 27639156