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.
Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/29622 |
Date | 25 August 2011 |
Creators | Shih, J. H. David |
Contributors | Huang, Annie |
Source Sets | University of Toronto |
Language | en_ca |
Detected Language | English |
Type | Thesis |
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