Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124

Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):126-132. doi: 10.1016/j.bbrc.2017.10.068. Epub 2017 Oct 16.

Abstract

Increasing evidences have revealed the important role of circular RNAs (circRNAs) in cardiovascular system disease. Whereas, the expression profiles and in-depth regulation of circRNAs on vascular smooth muscle cells (VSMCs) is still undetermined. In present study, our research team performed circRNAs microarray analysis to present the circRNAs expression profiles in high glucose induced VSMCs in vitro. Results showed that total of 983 circRNAs were discovered to be differentially expressed, and of these, 458 were upregulated and 525 were downregulated. Moreover, 31 circRNAs were up-regulated and 22 circRNAs were down-regulated with 2 fold change (P < 0.05). One of an up-regulated circRNA, circWDR77, was identified. In vitro cell assay, circWDR77 silencing significantly inhibited the proliferation and migration. Bioinformatics methods discovered that miR-124 and fibroblast growth factor 2 (FGF-2) were downstream targets of circWDR77. The RNA sequence complementary binding was validated by RNA immunoprecipitation (RIP) and/or luciferase reporter assay. Further function validation experiments revealed that circWDR77 regulated VSMCs proliferation and migration via targeting miR-124/FGF2. Taken together, present study firstly reveals the circRNAs expression profiles in high glucose induced VSMCs and identifies the role of circWDR77-miR-124-FGF2 regulatory pathway in VSMCs proliferation and migration, which might provide a new theoretical basis for diabetes mellitus correlated vasculopathy.

Keywords: Circular RNA; FGF2; Migration; Proliferation; Vascular smooth muscle cells; miR-124.

MeSH terms

  • Base Sequence
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / physiology*
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / physiology*
  • Oligonucleotide Array Sequence Analysis
  • RNA / genetics*
  • RNA / metabolism*
  • RNA, Circular
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*
  • Transcriptome

Substances

  • MIRN124 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Transcription Factors
  • WDR77 protein, human
  • Fibroblast Growth Factor 2
  • RNA