Neuroblastoma (NB) is a lethal tumor of childhood for which therapy has improved little over the past decades and which is assumed to benefit from insights into perturbed signaling pathways. Recently, new genetic components in the oncogenic signaling in NB cells have been discovered. Despite these advances, details of down stream signaling and the relationship between these pathways remain elusive. Such knowledge is however crucial for optimal design and monitoring of molecular therapy, such as prediction of respons to
therapy, design of multi-target molecular therapy to prevent resistance etc. MicroRNAs are important regulators of gene transcription and translation and have been recently shown to be implicated in cancer.
Moreover, we have demonstrated that they form intricate networks controlling expression of oncogenes and tumor suppressor. In this project, we wish to use our previous successful approach to establish the components of mRNA/miRNA regulatory networks implicated in NB oncogenesis. To this purpose, we will use cross species genomic analysis based on state-of-the-art genome/proteome wide analyses in the context of in vitro cellular model systems and mouse models combined with integrated genome and systems biology analyses.