Mechanism of MicroRNA miR-520g Pathogenesis in CNS-PNET

• Main Author: Shih, J. H. David
• Other Authors: Huang, Annie
• Language: en_ca
• Published: 2011
• Subjects: microRNA; brain tumour; cell cycle; development; 0307; 0992; 0715
• Online Access: http://hdl.handle.net/1807/29622

We recently discovered a high-level amplicon spanning the chr19q13.41 microRNA cluster in CNS Primitive Neuroectodermal Tumour, which results in striking upregulation of miR-520g. Constitutive over-expression of miR-520g in untransformed human neural stem cells enhanced cell growth, restricted differentiation down the neuronal lineage, and promoted expression of neural stem/progenitor cell markers. We thus hypothesize that ectopic miR-520g expression promotes tumourigenesis in part by inhibiting cellular differentiation. Consistent with this proposition, miR-520g is silenced upon embryonic stem cell differentiation and its expression is absent from most adult tissues. Moreover, expression analysis of miR-520g overexpressing cells revealed significant dysregulation of developmental signalling pathways. Further efforts focused on elucidating mechanisms of miR-520g function led to the identification of a cell cycle inhibitor, p21, as an important candidate target. These findings collectively suggest that miR-520g may modulate differentiation by regulating developmental signalling pathways and cell cycle exit of neural stem/progenitor cells.