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Role of microRNA-520h in 20(R)-ginsenoside-Rg3-mediated angiosuppression

  • Keung, Man-Hong (Department of Biology, Faculty of Science, Hong Kong Baptist University) ;
  • Chan, Lai-Sheung (Department of Biology, Faculty of Science, Hong Kong Baptist University) ;
  • Kwok, Hoi-Hin (Department of Biology, Faculty of Science, Hong Kong Baptist University) ;
  • Wong, Ricky Ngok-Shun (Department of Biology, Faculty of Science, Hong Kong Baptist University) ;
  • Yue, Patrick Ying-Kit (Department of Biology, Faculty of Science, Hong Kong Baptist University)
  • Received : 2015.05.04
  • Accepted : 2015.07.10
  • Published : 2016.04.15

Abstract

Background: Ginsenoside-Rg3, the pharmacologically active component of red ginseng, has been found to inhibit tumor growth, invasion, metastasis, and angiogenesis in various cancer models. Previously, we found that 20(R)-ginsenoside-Rg3 (Rg3) could inhibit angiogenesis. Since microRNAs (miRNAs) have been shown to affect many biological processes, they might play an important role in ginsenoside-mediated angiomodulation. Methods: In this study, we examined the underlying mechanisms of Rg3-induced angiosuppression through modulating the miRNA expression. In the miRNA-expression profiling analysis, six miRNAs and three miRNAs were found to be up- or down-regulated in vascular-endothelial-growth-factor-induced human-umbilical-vein endothelial cells (HUVECs) after Rg3 treatment, respectively. Results: A computational prediction suggested that mature hsa-miR-520h (miR-520h) targets ephrin receptor (Eph) B2 and EphB4, and hence, affecting angiogenesis. The up-regulation of miR-520h after Rg3 treatment was validated by quantitative real-time polymerase chain reaction, while the protein expressions of EphB2 and EphB4 were found to decrease, respectively. The mimics and inhibitors of miR- 520h were transfected into HUVECs and injected into zebra-fish embryos. The results showed that overexpression of miR-520h could significantly suppress the EphB2 and EphB4 protein expression, proliferation, and tubulogenesis of HUVECs, and the subintestinal-vessel formation of the zebra fish. Conclusion: These results might provide further information on the mechanism of Rg3-induced angiosuppression and the involvement of miRNAs in angiogenesis.

Keywords

References

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