The miR-183∼96∼182 cluster promotes tumorigenesis in a mouse model of medulloblastoma.

Medulloblastoma is the most common malignant pediatric brain tumor. Some are thought to originate from cerebellar granule neuron progenitors (CGNPs) that fail to undergo normal cell cycle exit and differentiation. The contribution of microRNAs to the initiation and progression of medulloblastoma remains poorly understood. Increased expression of the miR-183∼96∼182 cluster of microRNAs has been noted in several aggressive subgroups. We identified that expression of miR-183∼96∼182 was higher in medulloblastomas with Pten gene loss in the background of the activated sonic hedgehog (Shh) signaling pathway. Ectopic miR-183∼96∼182 expression in CGNPs synergized with exogenous Shh to increase proliferation and its role depended on hedgehog signaling activation. Our findings suggest a new microRNA cluster, the miR-183∼96∼182, functionally collaborates with the Shh signaling pathway in the development of medulloblastomas in mice.