Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma.
Small non-coding RNAs, in particular microRNAs(miRNAs), regulate fine-tuning of gene expression and can act as oncogenes or tumor suppressor genes. Differential miRNA 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(NB) is an embryonal tumor with highly variable clinical course. We analyzed the small RNA transcriptomes of five favorable and five unfavorable NBs using SOLiD next-generation sequencing, generating a total of >188 000 000 reads. MiRNA expression profiles obtained by deep sequencing correlated well with real-time PCR data. Cluster analysis differentiated between favorable and unfavorable NBs, and the miRNA transcriptomes of these two groups were significantly different. Oncogenic miRNAs of the miR17-92 cluster and the miR-181 family were overexpressed in unfavorable NBs. In contrast, the putative tumor suppressive microRNAs, miR-542-5p and miR-628, were expressed in favorable NBs and virtually absent in unfavorable NBs. 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 NBs.
Schulte
Johannes H
JH
University Children's Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. johannes.schulte@uni-due.de
Marschall
Tobias
T
Martin
Marcel
M
Rosenstiel
Philipp
P
Mestdagh
Pieter
P
Schlierf
Stefanie
S
Thor
Theresa
T
Vandesompele
Jo
J
Eggert
Angelika
A
Schreiber
Stefan
S
Rahmann
Sven
S
Schramm
Alexander
A
D001483:Base Sequence; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D015723:Gene Library; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D017393:RNA Editing; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
D035683:MicroRNAs; D012322:RNA Precursors
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