MicroRNA miR-93 Promotes Tumor Growth and Angiogenesis by Targeting integrin-β8

Oncogene. 2011 Feb 17;30(7):806-21. doi: 10.1038/onc.2010.465. Epub 2010 Oct 18.

Abstract

It has been reported that the miR-106b∼25 cluster, a paralog of the miR-17∼92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106b∼25 cluster is not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106b∼25 cluster, in angiogenesis and tumor formation. We found that miR-93 enhanced cell survival, promoted sphere formation and augmented tumor growth. Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation. In vivo studies revealed that miR-93-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities. Angiogenesis promoted by miR-93 in return facilitated cell survival, resulting in enhanced tumor growth. We further showed that integrin-β8 is a target of miR-93. Higher levels of integrin-β8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-β8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-β8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-β8 expression. Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Coculture Techniques
  • Endothelial Cells / metabolism
  • Gene Silencing
  • Humans
  • Integrin beta Chains / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Nervous System Neoplasms / metabolism
  • Nervous System Neoplasms / pathology*
  • RNA, Small Interfering / metabolism

Substances

  • Integrin beta Chains
  • MIRN93 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • integrin beta8