Neuroblastoma is the most common extracranial tumor of childhood. MYCN amplification is a common feature of aggressive tumor biology in neuroblastoma. The Nmyc transcription factor has been demonstrated to induce or repress expression of numerous genes. MicroRNAs (miRNA) are a recently discovered class of short RNAs that repress translation and promote mRNA degradation by sequence specific interaction with mRNA. Here, we sought to analyse the role of Nmyc in regulation of miRNA expression. Using a miRNA microarray containing 384 different miRNAs and a set of 160 miRNA real-time PCR assays to validate the microarray results, 7 miRNAs were identified to be induced by Nmyc in vitro and to be positively correlated with MYCN amplification in 28 primary neuroblastoma. Of these 7 miRNAs, miR-92, mir-106a and miR-17_5p belong to the miR-106a and miR-17 cluster, that have previously been shown to be regulated by c-myc in leukaemia. In addition, the miR-17-92 polycistron displays oncogenic properties in hematopoetic progenitor cells. We here provide first evidence of miRNA dysregulation in neuroblastoma, and propose a new mechanism by which Nmyc represses gene expression.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA