Targeting microRNA expression to regulate angiogenesis.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the post-transcriptional level by either degradation or translational repression of a target mRNA. More than 400 miRNAs have been identified in the human genome, but the relevance of most of them to physiological and pathological processes remains unclear. Although downregulation of the miRNA-processing enzymes Dicer and Drosha is known to impair angiogenesis, only a few specific miRNAs targeting endothelial cell function and angiogenesis have been identified. miR-221 and miR-222 block endothelial cell migration, proliferation and angiogenesis in vitro by targeting the stem cell factor receptor c-Kit and indirectly regulating expression of endothelial nitric oxide synthase. A pro-angiogenic function has been established for the miR-17-92 cluster, which promotes tumor angiogenesis in vivo. Expression of let7-f and miR-27b contributes to in vitro angiogenesis. We review recent studies on the involvement of miRNA in angiogenesis and discuss their implications for miRNA-based therapeutic strategies targeting this process in disease.
Kuehbacher
Angelika
A
Molecular Cardiology, Internal Medicine III, University of Frankfurt, 60590 Frankfurt, Germany.
Urbich
Carmen
C
Dimmeler
Stefanie
S
D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000502:physiology
D035683:MicroRNAs