High Expression of NcRAN, a Novel Non-coding RNA Mapped to Chromosome 17q25.1, is Associated with Poor Prognosis in Neuroblastoma

Neuroblastoma shows complex patterns of genetic aberrations including MYCN amplification, deletion of chromosome 1p or 11q, and gain of chromosome 17q. The 17q gain is frequently observed in high-risk neuroblastomas, however, the candidate genes still remain elusive. In the present study, we integrated the data of comparative genomic hybridization of 236 tumors by BAC array and expression profiling of 136 tumors by using the in-house cDNA microarray carrying 5,340 genes derived from primary neuroblastomas. A novel candidate gene mapped to chromosome 17q25.1 with two splicing variants, Nbla10727 and Nbla12061, was identified. The transcript size appeared to be 2.3 kb by Northern blot, however, the cDNA sequences had no obvious open reading frame. The protein product was undetectable by both in vivo and in vitro translation assays, suggesting that the transcript might not encode any protein product. Therefore, we named it as ncRAN (non-coding RNA expressed in aggressive neuroblastoma). In analysis of 70 patients with sporadic neuroblastoma, the high levels of ncRAN mRNA expression were significantly associated with poor outcome of the patients (p<0.001). The multivariate analysis showed that expression of ncRAN mRNA was an independent prognostic factor among age, stage, origin and MYCN expression. Ectopic expression of ncRAN induced transformation of NIH3T3 cells in soft agar, while knockdown of endogenous ncRAN with RNA interference significantly inhibited cell growth in SH-SY5Y cells. Collectively, our results suggest that ncRAN may be a novel non-coding RNA mapped to the region of 17q gain and act like an oncogene in aggressive neuroblastomas.