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

• Published in: European journal of cell biology 2017-12, Vol.96 (8), p.758-766
• Main Authors: Bartoszewski, Rafal, Serocki, Marcin, Janaszak-Jasiecka, Anna, Bartoszewska, Sylwia, Kochan-Jamrozy, Kinga, Piotrowski, Arkadiusz, Króliczewski, Jarosław, Collawn, James F.
• Format: Article
• Language: English
• Subjects: Cell Hypoxia - genetics; Down-Regulation; HIF-1; HIF-2; hsa-miR-200b-3p; Human Umbilical Vein Endothelial Cells; Humans; HUVEC; KLF2; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Micro-RNA 200b; MicroRNAs - genetics; MicroRNAs - metabolism; Neovascularization, Physiologic - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transfection
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1016/j.ejcb.2017.10.001

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.