Please use this identifier to cite or link to this item:
Title: Impact of DICER1 and DROSHA on the angiogenic capacity of human endothelial cells
Author(s): Braun, Heike
Hauke, Michael
Ripperger, Anne
Ihling, Christian
Fuszard, Matthew
Eckenstaler, Robert
Benndorf, RalfLook up in the Integrated Authority File of the German National Library
Issue Date: 2021
Type: Article
Language: English
Abstract: RNAi-mediated knockdown of DICER1 and DROSHA, enzymes critically involved in miRNA biogenesis, has been postulated to affect the homeostasis and the angiogenic capacity of human endothelial cells. To re-evaluate this issue, we reduced the expression of DICER1 or DROSHA by RNAi-mediated knockdown and subsequently investigated the effect of these interventions on the angiogenic capacity of human umbilical vein endothelial cells (HUVEC) in vitro (proliferation, migration, tube formation, endothelial cell spheroid sprouting) and in a HUVEC xenograft assay in immune incompetent NSGTM mice in vivo. In contrast to previous reports, neither knockdown of DICER1 nor knockdown of DROSHA profoundly affected migration or tube formation of HUVEC or the angiogenic capacity of HUVEC in vivo. Furthermore, knockdown of DICER1 and the combined knockdown of DICER1 and DROSHA tended to increase VEGF-induced BrdU incorporation and induced angiogenic sprouting from HUVEC spheroids. Consistent with these observations, global proteomic analyses showed that knockdown of DICER1 or DROSHA only moderately altered HUVEC protein expression profiles but additively reduced, for example, expression of the angiogenesis inhibitor thrombospondin-1. In conclusion, global reduction of miRNA biogenesis by knockdown of DICER1 or DROSHA does not inhibit the angiogenic capacity of HUVEC. Further studies are therefore needed to elucidate the influence of these enzymes in the context of human endothelial cell-related angiogenesis.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Publikationsfonds MLU
Journal Title: International journal of molecular sciences
Publisher: Molecular Diversity Preservation International
Publisher Place: Basel
Volume: 22
Issue: 18
Original Publication: 10.3390/ijms22189855
Appears in Collections:Open Access Publikationen der MLU

Files in This Item:
File Description SizeFormat 
ijms-22-09855.pdf2.87 MBAdobe PDFThumbnail