Targeting of expression allows the identification of drugs effective in counteracting neuroblastoma cell growth.

The pathogenic role of the gene in neuroblastoma is indicated by heterozygous mutations in neuroblastoma patients and by gene overexpression in both neuroblastoma cell lines and tumor samples. encodes a transcription factor which is crucial for the correct development and differentiation of sympathetic neurons. overexpression is considered a prognostic marker for neuroblastoma and it is also used by clinicians to monitor minimal residual disease. Furthermore, it has been observed that neuronal differentiation in neuroblastoma is dependent on down-regulation of expression, which confirms that PHOX2B expression may be considered a target in neuroblastoma. Here, promoter or 3' untranslated region were used as molecular targets in an high-throughput approach that led to the identification of molecules able to decrease expression at transcriptional and likely even at post-transcriptional levels. Further functional investigations carried out on mRNA levels and biological consequences, such as neuroblastoma cell apoptosis and growth, showed that chloroquine and mycophenolate mofetil are most promising agents for neuroblastoma therapy based on down-regulation of expression. Finally, a strong correlation between the effect of drugs in terms of down-regulation of expression and of biological consequences in neuroblastoma cells confirms the role of as a potential molecular target in neuroblastoma.