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Expression of miR-124 inhibits growth of medulloblastoma cells.

  • Author(s): Silber, Joachim
  • Hashizume, Rintaro
  • Felix, Tristan
  • Hariono, Sujatmi
  • Yu, Mamie
  • Berger, Mitchel S
  • Huse, Jason T
  • VandenBerg, Scott R
  • James, C David
  • Hodgson, J Graeme
  • Gupta, Nalin
  • et al.
Abstract

Medulloblastoma is the most common malignant brain tumor in children, and a substantial number of patients die as a result of tumor progression. Overexpression of CDK6 is present in approximately one-third of medulloblastomas and is an independent poor prognostic marker for this disease. MicroRNA (miR)-124 inhibits expression of CDK6 and prevents proliferation of glioblastoma and medulloblastoma cells in vitro. We examined the effects of miR-124 overexpression on medulloblastoma cells both in vitro and in vivo and compared cell lines that have low and high CDK6 expression. MiR-124 overexpression inhibits the proliferation of medulloblastoma cells, and this effect is mediated mostly through the action of miR-124 upon CDK6. We further show that induced expression of miR-124 potently inhibits growth of medulloblastoma xenograft tumors in rodents. Further testing of miR-124 will help define the ultimate therapeutic potential of preclinical models of medulloblastoma in conjunction with various delivery strategies for treatment.

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