MicroRNA-16 affects key functions of human endothelial progenitor cells

Emeline Goretti, Magali Rolland-Turner, Frédérique Léonard, Lu Zhang, Daniel R. Wagner, Yvan Devaux*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

The capacity of EPCs to repair injured tissues is limited. The role of miRNAs in EPCs is largely unknown. We tested whether miRNAs may be useful to enhance the regenerative capacity of EPCs. Early EPCs were isolated from human PBMCs, and late EPCs were amplified from enriched human peripheral CD34+ cells. Expression profiles of miRNAs and mRNAs were obtained by microarrays. Among the miRNAs differentially expressed between early and late EPCs, five members of the miR-16 family (miR-15a/-15b/-16/-103/-107) were overexpressed in early EPCs. Web-accessible databases predicted 375 gene targets for these five miRNAs. Among these, two regulators of cell cycle progression (CCND1 and CCNE1) and one associated gene (CDK6) were less expressed in early EPCs. Administration of anti-miR-16 in early EPCs enhanced the expression of these three genes, and administration of premiR- 16 in late EPCs decreased their expression. In early EPCs, antagonism of miR-16 allowed for cell-cycle re-entry, stimulated differentiation, enhanced IL-8 secretion, and promoted the formation of capillary-like structures by HUVECs. In conclusion, miR-16 regulates key biological pathways in EPCs. This may have important implications to enhance the capacity of EPCs to repair injured tissues.

Original languageEnglish
Pages (from-to)645-655
Number of pages11
JournalJournal of Leukocyte Biology
Volume93
Issue number5
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Cell cycle
  • Cell differentiation
  • Microarrays
  • Transcriptomic

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