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Home › Dataset Library › OTX2 drives medulloblastoma proliferation via direct regulation of cell cycle genes and inhibits differentiation

Dataset: OTX2 drives medulloblastoma proliferation via direct regulation of cell cycle genes and inhibits differentiation

The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in...

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The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients. Keywords: OTX2, medulloblastoma, mRNA profiling *** This Series represents the gene expression component of the study. Three independent time course experiments of OTX2 silencing, and 1 control experiment in D425 medulloblastoma cells.

Species:
human

Samples:
24

Source:
E-GEOD-22875

PubMed:
21964830

Updated:
Dec.12, 2014

Registered:
Sep.15, 2014


Factors: (via ArrayExpress)
Sample TIME COURSE PROTOCOL TIME
GSM565176 1 doxycyline inducible shRNA against OTX2 0 hrs
GSM565177 1 doxycyline inducible shRNA against OTX2 8 hrs
GSM565178 1 doxycyline inducible shRNA against OTX2 16 hrs
GSM565179 1 doxycyline inducible shRNA against OTX2 24 hrs
GSM565180 1 doxycyline inducible shRNA against OTX2 48 hrs
GSM56518 1 doxycyline inducible shRNA against OTX2 96 hrs
GSM565182 2 doxycyline inducible shRNA against OTX2 0 hrs
GSM565183 2 doxycyline inducible shRNA against OTX2 8 hrs
GSM565184 2 doxycyline inducible shRNA against OTX2 16 hrs
GSM565185 2 doxycyline inducible shRNA against OTX2 24 hrs
GSM565186 2 doxycyline inducible shRNA against OTX2 48 hrs
GSM565187 2 doxycyline inducible shRNA against OTX2 96 hrs
GSM565188 3 doxycyline inducible shRNA against OTX2 0 hrs
GSM565189 3 doxycyline inducible shRNA against OTX2 8 hrs
GSM565190 3 doxycyline inducible shRNA against OTX2 16 hrs
GSM56519 3 doxycyline inducible shRNA against OTX2 24 hrs
GSM565192 3 doxycyline inducible shRNA against OTX2 48 hrs
GSM565193 3 doxycyline inducible shRNA against OTX2 96 hrs
GSM565194 not specified control 0 hrs
GSM565195 not specified control 8 hrs
GSM565196 not specified control 16 hrs
GSM565197 not specified control 24 hrs
GSM565198 not specified control 48 hrs
GSM565199 not specified control 96 hrs

Tags

  • brain
  • cell
  • cerebellum
  • medulloblastoma

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