Our results suggest that enhanced MYCN expression in human neuroblastoma cells alters the angiogenic balance by down-regulating endothelial cell growth inhibitors but leaving the expression of the stimulators unaffected.
MYCN, for example, which is a mutated gene of NB, is targeted by hsa-miR-29a and hsa-miR-34a, and regulates another eight differentially-expressed miRNAs that target genes VEGFA, BCL2, REL2 and so on.
Event-free survival and overall survival were significantly poorer for patients with 11q loss in the whole cohort (event-free survival and overall survival, P < 0.001) and in different subsets: neuroblastoma without MYCN amplification (MNA) (event-free survival and overall survival, P < 0.001), with MNA (event-free survival, P = 0.03; overall survival, P = 0.02), and MYCN-nonamplified stage 1, 2, 3, and 4S tumors with and without del 1p (event-free survival and overall survival, P < 0.001).
One of the major causes of sporadic NB is known to be MYCN amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible for familial NB.
To gain an insight into the distribution of MYCN binding and to identify clinically relevant MYCN target genes, we performed an integrated analysis of MYCN ChIP-chip and mRNA expression using the MYCN repressible SHEP-21N neuroblastoma cell line.
A well-known example is neuroblastoma for which MYCN gene (v-myc myelocytomatosis viral-related oncogene) amplification has a relevant prognostic significance.
The PI, MYCN status, International Neuroblastoma Staging System (INSS) stage, International Neuroblastoma Pathology Classification grade, Hughes grade, and the patients' age at diagnosis were all found to be significant predictors of event free survival by univariate Kaplan-Meier analysis.
This growth effect was accompanied by a marked decrease in the expression of MYC, MYCN, AKT and an increase in p53 expression in neuroblastoma cell lines without TP53 mutation.
Besides some well described and prognostic genetic findings in NB as MYCN amplification, gain on 17q and losses on 9q and 11q23, we report an unusual deletion involving 8q region in this disease.
Evaluations of N-myc gene amplification and DNA ploidy are complementary, and the combined determination of these two factors may be one of the most powerful prognostic indicators in neuroblastoma.
The aim of this study was to determine whether children with neuroblastoma in which MYCN oncogene amplification is manifested as HSRs at diagnosis have a worse prognosis than those whose tumors exhibit dmins.
Recently, a mathematical model was used to demonstrate that the network regulating stress signaling by the c-Jun N-terminal kinase pathway played a crucial role in survival of patients with neuroblastoma irrespective of their MYCN amplification status.
Dual targeting of wild-type and mutant p53 by small molecule RITA results in the inhibition of N-Myc and key survival oncogenes and kills neuroblastoma cells in vivo and in vitro.
These observations confirm the juxtaposition of 17q material with MYCN sequences in some neuroblastomas, and imply that there may be a physical or functional relationship between these two features in MYCN amplified neuroblastoma.
Together, this implies that deregulated MYCN protein levels in MYCN-amplified neuroblastoma cells activate SKP2 through CDK4 induction, abrogating repressive pRB-E2F1 complexes bound to the SKP2 promoter.
Aminoacylase expression was examined in TrkB-positive, MYCN-amplified (SMS-KCNR and SK-N-BE) and TrkB-negative, non-MYCN-amplified (SK-N-AS, SK-N-SH, SH-SY5Y and SH-EP) neuroblastoma cell lines.