Up-regulation of FGFBP1 signaling contributes to miR-146a-induced angiogenesis in human umbilical vein endothelial cells

Sci Rep. 2016 Apr 28;6:25272. doi: 10.1038/srep25272.

Abstract

Recent microRNA expression profiling studies have documented an up-regulation of miR-146a in several angiogenesis models. However, the underlying molecular mechanism of miR-146a in the angiogenic activity of endothelial cells has not been clearly elucidated. The present study was aimed to evaluate whether miR-146a promotes angiogenesis in HUVECs by increasing FGFBP1 expression via directly targeting CREB3L1. miR-146a was over expressed in HUVECs via lentiviral-miR-146a. Expression profiling analysis found miR-146a over expression resulted in up-regulation of angiogenesis and cytokine activity associated genes including FGF2. Further a combination of bioinformatics and experimental analyses demonstrated the CREB3L1 as a bona fide functional target of miR-146a during angiogenesis. Moreover, CREB3L1 inhibited luciferase expression from FGFBP1 promoter containing only CRE elements. Furthermore, CREB3L1 inhibited FGFBP1 expression by binding to two CRE-like sites located at approximately -1780-1777 and -868-865 bp relative to the FGFBP1 transcription start site. Additionally, ectopic expression of CREB3L1 decreased miR-146a-induced FGF2 secretion. These findings indicate that the miR-146a-CREB3L1-FGFBP1 signaling axis plays an important role in the regulation of angiogenesis in HUVECs and provides a potential therapeutic target for anti-angiogenic therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cytokines / metabolism
  • Human Umbilical Vein Endothelial Cells / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / metabolism*
  • Neovascularization, Physiologic*
  • Nerve Tissue Proteins / metabolism*
  • Signal Transduction*
  • Up-Regulation*

Substances

  • CREB3L1 protein, human
  • Carrier Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • MIRN146 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • FGFBP1 protein, human