miR-200b downregulates Kruppel Like Factor 2 (KLF2) during acute hypoxia in human endothelial cells

Academic Article

Abstract

  • ¬© 2017 Elsevier GmbH 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.
  • Published In

  • Cytobiologie  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bartoszewski R; Serocki M; Janaszak-Jasiecka A; Bartoszewska S; Kochan-Jamrozy K; Piotrowski A; Kr√≥liczewski J; Collawn JF
  • Start Page

  • 758
  • End Page

  • 766
  • Volume

  • 96
  • Issue

  • 8