MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-β8

L. Fang, Z. Deng, T. Shatseva, J. Yang, C. Peng, W. W. Du, A. J. Yee, L. C. Ang, C. He, S. W. Shan, B. B. Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

248 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)806-821
Number of pages16
JournalOncogene
Volume30
Issue number7
DOIs
Publication statusPublished - 17 Feb 2011
Externally publishedYes

Keywords

  • angiogenesis
  • integrin
  • microRNA
  • siRNA
  • tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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