MicroRNA-217 promotes angiogenesis of human cytomegalovirus-infected endothelial cells through downregulation of SIRT1 and FOXO3A

PLoS One. 2013 Dec 20;8(12):e83620. doi: 10.1371/journal.pone.0083620. eCollection 2013.

Abstract

Human cytomegalovirus(HCMV) infection has been shown to contribute to vascular disease through the induction of angiogenesis. However, the role of microRNA in angiogenesis induced by HCMV infection remains unclear. The present study was thus designed to explore the potential effect of miR-1217 on angiogenesis and to disclose the underlying mechanism in endothelial cells. We found that HCMV infection of endothelial cells(ECs) enhanced expression of miR-217 and reduced SIRT1 and FOXO3A protein level in 24 hours post infection(hpi). Transfection of miR-217 inhibitor not only depressed cellular migration and tube formation induced by HCMV infection, but also enhanced SIRT1 and FOXO3A protein expression. Additionally, luciferase assay confirmed that miR-217 directly targeted FOXO3A mRNA 3`UTR. Furthermore, pretreatment with resveratrol depressed motility and tube formation of HCMV-infected ECs, which could be reversed by SIRT1 siRNA. Similarly, delivery of FOXO3A overexpression lentivirus suppressed proliferative rate, migration and tube formation of HCMV-infected ECs, which reversed by transfection of FOXO3A siRNA. In summary, HCMV infection of endothelial cells induces angiogenesis by both of miR-217/SIRT1 and miR-217/FOXO3A axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cytomegalovirus / physiology*
  • Down-Regulation / genetics*
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / genetics*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / virology*
  • Humans
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics*
  • Sirtuin 1 / genetics*

Substances

  • 3' Untranslated Regions
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • MIRN217 microRNA, human
  • MicroRNAs
  • SIRT1 protein, human
  • Sirtuin 1

Grants and funding

The work was supported by Beijing Natural Science Foundation (NOs. 7102040,7132060), National Natural Science Foundation of China (NOs. 81041020, 81271311 and 81241039), Traditional Chinese Medicine, Beijing Technology Development Fund (NO. SF-2007-III-22), Beijing Excellent Talent Foundation (NO. 20071-D0300100062), high-level technical training project funding of Beijing health system (2011-3-004) and Beijing city staff to go abroad preferential funding scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.