miRNA Expression Profiling of Murine Neuroblastoma Figure 3. Analysis of human and mouse samples based on miRNAs (n = 43) deregulated in human MNA. (A) Hierarchical clustering (n = 43). Cluster ‘‘Mouse’’ contains all the mouse samples, split in two branches ‘‘Tumors’’ and controls ‘‘Adrenals’’. Cluster ‘‘Human’’ includes all the human samples split in two branches which shows an enrichment (p,0.05) for MNA tumors (59.5%, in cluster ‘‘MNA’’) and an under-representation of MNA samples (12.9%, in cluster ‘‘non-MNA’’), respectively. (B) Principal component analysis. Line ‘‘a’’ splits the samples based on the species: human (left) and mouse (right). Line ‘‘b’’ shows a distribution of the samples according to MYCN expression: a clear split in the mouse and an enrichment (p,0.001) for human MNA samples (under). Mouse tumors (green), mouse adrenals (black), human MNA (red) and human non-MNA (purple). doi:10.1371/journal.pone.0028356.g003 primary tumors, but is often mutated in recurrent tumors. Although the p53 transcription factor is known to regulate a number of miRNAs, including miR-34a, miR-23b, miR-26, miR-30, miR-107 and miR-192 [40–45], there was very little difference in miRNA expression patterns between tumors derived from p53 wild-type TH-MYCN versus p53 mutant TH-MYCN mice, despite significant differences in tumor phenotype when MYCN drives neuroblastoma in a p53 deficient background [25]. This implies that p53 mediated regulation of miRNAs requires complete abrogation of p53 activity rather than p53 haploinsufficiency. Certainly this was the case for p53 regulation of miR-34a, where the effects of p53 PLoS ONE | www.plosone.org 6 December 2011 | Volume 6 | Issue 12 | e28356