De-repression of CTGF via the miR-17-92 cluster upon differentiation of human glioblastoma spheroid cultures

  • Ernst A
  • Campos B
  • Meier J
 et al. 
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Abstract

All-trans retinoic acid is a potent promoter of cellular differentiation processes, which is used in cancer therapy. Glioblastoma spheroid cultures are enriched in tumor-initiating cells, and provide a model to test new treatment options in vitro. We investigated the molecular mechanisms of response to exposure to differentiation-promoting conditions in such cultures. Microarray analyses of five independent cultures showed that after induction of differentiation, inhibitors of transforming growth factor-beta/bone morphogenetic protein, Wnt/beta-catenin and IGF signaling were upregulated, whereas expression of several microRNAs decreased, particularly that of the miR-17-92 cluster. In primary astrocytic gliomas (n=82), expression of several members of miR-17-92 was significantly higher relative to those of normal brain (n=8) and significantly increased with tumor grade progression (P

Author-supplied keywords

  • CTGF
  • Glioblastoma
  • MiR-17-92
  • Retinoic acid
  • Spheroid culture

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