N-myc and Noncoding RNAs in Neuroblastoma

Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Amplification and overexpression of the MYCN proto-oncogene occurs in approximately 20% of neuroblastomas and is associated with advanced stage disease, rapid tumor progression, and poor prognosis. MYCN encodes the transcriptional regulator N-myc, which has been shown to both up- and downregulate many target genes involved in cell cycle, DNA damage, differentiation, and apoptosis in neuroblastoma. During the last years, it has become clear that N-myc also modulates the expression of several classes of noncoding RNAs, in particular microRNAs. MicroRNAs are the most widely studied noncoding RNA molecules in neuroblastoma. They function as negative regulators of gene expression at the posttranscriptional level in diverse cellular processes. Aberrant regulation of miRNA expression has been implicated in the pathogenesis of neuroblastoma. While the N-myc protein is established as an important regulator of several miRNAs involved in neuroblastoma tumorigenesis, tumor suppressor miRNAs have also been documented to repress MYCN expression and inhibit cell proliferation of MYCN-amplified neuroblastoma cells. It is now becoming increasingly evident that N-myc also regulates the expression of long noncoding RNAs such as T-UCRs and ncRAN. This review summarizes the current knowledge about the interplay between N-myc and noncoding RNAs in neuroblastoma and how this contributes to neuroblastoma tumorigenesis. Mol Cancer Res; 10(10); 1243-53. (C) 2012 AACR.