Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation

J. G. Cui, Y. Zhao, P. Sethi, Y. Y. Li, A. Mahta, F. Culicchia, W. J. Lukiw

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63 Scopus citations

Abstract

High density micro-RNA (miRNA) arrays, fluorescent-reporter miRNA assay and Northern miRNA dot-blot analysis show that a brain-enriched miRNA-128 is significantly down-regulated in glioblastoma multiforme (GBM) and in GBM cell lines when compared to age-matched controls. The down-regulation of miRNA-128 was found to inversely correlate with WHO tumor grade. Three bioinformatics-verified miRNA-128 targets, angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6), a transcription suppressor that promotes stem cell renewal and inhibits the expression of known tumor suppressor genes involved in senescence and differentiation, Bmi-1, and a transcription factor critical for the control of cell-cycle progression, E2F-3a, were found to be up-regulated. Addition of exogenous miRNA-128 to CRL-1690 and CRL-2610 GBM cell lines (a) restored 'homeostatic' ARP5 (ANGPTL6), Bmi-1 and E2F-3a expression, and (b) significantly decreased the proliferation of CRL-1690 and CRL-2610 cell lines. Our data suggests that down-regulation of miRNA-128 may contribute to glioma and GBM, in part, by coordinately up-regulating ARP5 (ANGPTL6), Bmi-1 and E2F-3a, resulting in the proliferation of undifferentiated GBM cells.

Original languageEnglish (US)
Pages (from-to)297-304
Number of pages8
JournalJournal of neuro-oncology
Volume98
Issue number3
DOIs
StatePublished - Jul 2010

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Keywords

  • ARP5 (ANGPTL6)
  • Bmi-1
  • Cell-cycle control
  • Differentiation
  • Differentiation regulated transcription factors (DRTFs)
  • E2F-3
  • Glioblastoma multiforme (GBM)
  • Micro-RNA array
  • miRNA-128
  • Neural stem cell (NSC)
  • NSC renewal

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

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