Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4

  • Authors:
    • Yi-Ze Li
    • Lei Wen
    • Xu Wei
    • Qian-Rong Wang
    • Long-Wen Xu
    • Hong-Mei Zhang
    • Wen-Chao Liu
  • View Affiliations

  • Published online on: July 5, 2016     https://doi.org/10.3892/or.2016.4912
  • Pages: 1569-1575
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Abstract

Recent lentiviral-based microRNA (miRNA) library screening has identified miRNA-7 (miR-7) as an anti‑angiogenic miRNA in human umbilical vein endothelial cells (HUVECs). However, the underlying mechanism of miR-7 in the suppression of angiogenesis remains largely unknown. In the present study, we report that miR-7 inhibition promoted angiogenesis by upregulating vascular endothelial growth factor (VEGF) and directly targeting Krüppel-like factor 4 (KLF4). Downregulation of miR-7 promoted tube formation of HUVECs, accompanied by upregulation of mRNA and protein levels of both VEGF and KLF4. miR-7 directly targeted KLF4 as demonstrated by luciferase reporter assay and miR-7 mimics decreased KLF4. Furthermore, bioinformatic analysis revealed the presence of multiple DNA-binding elements of KLF4 in the VEGF promoter. Chromatin immunoprecipitation (ChIP) demonstrated that the KLF4 antibody specifically pulled down the VEGF promoter in the HUVECs. Furthermore, ectopic overexpression of KLF4 induced VEGF mRNA and protein levels. In addition, KLF4 silencing inhibited the angiogenesis induced by the miR-7 inhibitor in the HUVECs. Our results demonstrated that KLF4 is a direct target of miR-7 and a transcription activator of VEGF. These findings indicate that the miR-7-KLF4-VEGF signaling axis plays an important role in the regulation of angiogenesis in HUVECs, suggesting that miR-7 is a potential agent for the development of anti-angiogenic therapeutics in vascular diseases and solid tumors.
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September-2016
Volume 36 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li Y, Wen L, Wei X, Wang Q, Xu L, Zhang H and Liu W: Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4. Oncol Rep 36: 1569-1575, 2016
APA
Li, Y., Wen, L., Wei, X., Wang, Q., Xu, L., Zhang, H., & Liu, W. (2016). Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4. Oncology Reports, 36, 1569-1575. https://doi.org/10.3892/or.2016.4912
MLA
Li, Y., Wen, L., Wei, X., Wang, Q., Xu, L., Zhang, H., Liu, W."Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4". Oncology Reports 36.3 (2016): 1569-1575.
Chicago
Li, Y., Wen, L., Wei, X., Wang, Q., Xu, L., Zhang, H., Liu, W."Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4". Oncology Reports 36, no. 3 (2016): 1569-1575. https://doi.org/10.3892/or.2016.4912