Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8469727 | European Journal of Cell Biology | 2017 | 9 Pages |
Abstract
The role of microRNAs in controlling angiogenesis is recognized as a promising therapeutic target in both cancer and cardiovascular disorders. However, understanding a miRNA's pleiotropic effects on angiogenesis is a limiting factor for these types of therapeutic approaches. Using genome-wide next-generation sequencing, we examined the role of an antiangiogenic miRNA, miR-200b, in primary human endothelial cells. The results indicate that miR-200b has complex effects on hypoxia-induced angiogenesis in human endothelia and importantly, that many of the reported miR-200b effects using miRNA overexpression may not be representative of the physiological role of this miRNA. We also identified the antiangiogenic KLF2 gene as a novel target of miR-200b. Our studies indicate that the physiological changes in miR-200b levels during acute hypoxia may actually have a proangiogenic effect through Klf2 downregulation and subsequent stabilization of HIF-1 signaling. Moreover, we provide a viable approach for differentiating direct from indirect miRNA effects in order to untangle the complexity of individual miRNA networks.
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Authors
Rafal Bartoszewski, Marcin Serocki, Anna Janaszak-Jasiecka, Sylwia Bartoszewska, Kinga Kochan-Jamrozy, Arkadiusz Piotrowski, JarosÅaw Króliczewski, James F. Collawn,