Abstract

Small non-coding RNAs, in particular microRNAs, regulate fine-tuning of gene expression and can act as oncogenes or tumor suppressor genes. Differential microRNA expression has been reported to be of functional relevance for tumor biology. Using next-generation sequencing, the unbiased and absolute quantification of the small RNA transcriptome is now feasible. Neuroblastoma is an embryonal tumor with highly variable clinical course. We analyzed the small RNA transcriptomes of five favorable and five unfavorable neuroblastomas using SOLiD next-generation sequencing, generating a total of 188,000,000 reads. MicroRNA expression profiles obtained by deep sequencing correlated well with real-time PCR data. Cluster analysis differentiated between favorable and unfavorable neuroblastomas, and the microRNA transcriptomes of these two groups were significantly different. Oncogenic microRNAs of the miR17-92 cluster and the miR-181 family were overexpressed in unfavorable neuroblastomas. In contrast, the putative tumor suppressive microRNAs, miR-542-5p and miR-628, were expressed in favorable neuroblastomas and virtually absent in unfavorable neuroblastomas. In-depth sequence analysis revealed extensive post-transcriptional miRNA editing. Of 13 identified novel miRNAs, three were further analyzed, and expression could be confirmed in a cohort of 70 neuroblastomas.

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