Details

Autor(en) / Beteiligte

• NORTHCOTT, Paul A
• FERNANDEZ-L, Africa
• KENNEY, Anna Marie
• TAYLOR, Michael D
• HAGAN, John P
• ELLISON, David W
• GRAJKOWSKA, Wesia
• GILLESPIE, Yancey
• GRUNDY, Richard
• VAN METER, Timothy
• RUTKA, James T
• CROCE, Carlo M

Titel

The miR-17/92 Polycistron Is Up-regulated in Sonic Hedgehog-Driven Medulloblastomas and Induced by N-myc in Sonic Hedgehog-Treated Cerebellar Neural Precursors

Ist Teil von

• Cancer research (Chicago, Ill.), 2009-04, Vol.69 (8), p.3249-3255

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Medulloblastoma is the most common malignant pediatric brain tumor, and mechanisms underlying its development are poorly understood. We identified recurrent amplification of the miR-17/92 polycistron proto-oncogene in 6% of pediatric medulloblastomas by high-resolution single-nucleotide polymorphism genotyping arrays and subsequent interphase fluorescence in situ hybridization on a human medulloblastoma tissue microarray. Profiling the expression of 427 mature microRNAs (miRNA) in a series of 90 primary human medulloblastomas revealed that components of the miR-17/92 polycistron are the most highly up-regulated miRNAs in medulloblastoma. Expression of miR-17/92 was highest in the subgroup of medulloblastomas associated with activation of the sonic hedgehog (Shh) signaling pathway compared with other subgroups of medulloblastoma. Medulloblastomas in which miR-17/92 was up-regulated also had elevated levels of MYC/MYCN expression. Consistent with its regulation by Shh, we observed that Shh treatment of primary cerebellar granule neuron precursors (CGNP), proposed cells of origin for the Shh-associated medulloblastomas, resulted in increased miR-17/92 expression. In CGNPs, the Shh effector N-myc, but not Gli1, induced miR-17/92 expression. Ectopic miR-17/92 expression in CGNPs synergized with exogenous Shh to increase proliferation and also enabled them to proliferate in the absence of Shh. We conclude that miR-17/92 is a positive effector of Shh-mediated proliferation and that aberrant expression/amplification of this miR confers a growth advantage to medulloblastomas.