title: Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma.
abstract: 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.
authors.affiliation: University Children's Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. johannes.schulte@uni-due.de
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.forename: Tobias
authors.initials: T
authors.lastname: Marschall
authors.forename: Marcel
authors.initials: M
authors.lastname: Martin
authors.forename: Philipp
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schlierf
authors.forename: Theresa
authors.initials: T
authors.lastname: Thor
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Sven
authors.initials: S
authors.lastname: Rahmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
mesh_terms: 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
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors
references.citation: Cancer Res. 2007 Feb 1;67(3):976-83
references.pmid: 17283129
references.citation: Clin Chem. 2009 Apr;55(4):611-22
references.pmid: 19246619
references.citation: Curr Pharm Des. 2009;15(4):456-62
references.pmid: 19199973
references.citation: Genome Res. 2010 Feb;20(2):257-64
references.pmid: 20051556
references.citation: Nat Rev Cancer. 2006 Apr;6(4):259-69
references.pmid: 16557279
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D154-8
references.pmid: 17991681
references.citation: Cancer Lett. 2009 Feb 8;274(1):10-5
references.pmid: 18639376
references.citation: Oncogene. 2007 Jul 26;26(34):5017-22
references.pmid: 17297439
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D89-92
references.pmid: 18948287
references.citation: Lancet. 2007 Jun 23;369(9579):2106-20
references.pmid: 17586306
references.citation: Int J Cancer. 2008 Feb 1;122(3):699-704
references.pmid: 17943719
references.citation: EMBO Rep. 2007 Aug;8(8):763-9
references.pmid: 17599088
references.citation: Genes Dev. 2009 Feb 15;23(4):433-8
references.pmid: 19240131
references.citation: Genome Biol. 2009;10(6):R64
references.pmid: 19531210
references.citation: Clin Cancer Res. 2009 Sep 1;15(17):5560-8
references.pmid: 19706822
references.citation: BMC Genomics. 2008 Jan 29;9:52
references.pmid: 18230126
references.citation: Cytogenet Genome Res. 2005;110(1-4):462-7
references.pmid: 16093699
references.citation: Oncogene. 2010 Mar 4;29(9):1394-404
references.pmid: 19946337
references.citation: Nature. 2005 Jun 9;435(7043):828-33
references.pmid: 15944707
references.citation: Nat Biotechnol. 2008 Apr;26(4):407-15
references.pmid: 18392026
references.citation: PLoS One. 2008 May 21;3(5):e2236
references.pmid: 18493594
references.citation: Genome Res. 2008 Apr;18(4):610-21
references.pmid: 18285502
references.citation: Lancet Oncol. 2003 Aug;4(8):472-80
references.pmid: 12901961
references.citation: FASEB J. 2009 Dec;23(12):4276-87
references.pmid: 19713529
references.citation: Nature. 2005 Jun 9;435(7043):839-43
references.pmid: 15944709
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3687-92
references.pmid: 16505370
references.citation: BMC Med Genomics. 2009 Jun 09;2:35
references.pmid: 19508715
references.citation: Science. 2001 Oct 26;294(5543):858-62
references.pmid: 11679671
references.citation: Nat Methods. 2009 Jul;6(7):474-6
references.pmid: 19564845
references.citation: Science. 2007 Feb 23;315(5815):1137-40
references.pmid: 17322061
references.citation: Nat Cell Biol. 2009 Sep;11(9):1157-63
references.pmid: 19701194
references.citation: Cell. 2007 Jun 29;129(7):1401-14
references.pmid: 17604727
references.citation: Nat Rev Cancer. 2003 Mar;3(3):203-16
references.pmid: 12612655
references.citation: Mol Cancer Res. 2008 May;6(5):735-42
references.pmid: 18505919
references.citation: Nucleic Acids Res. 2008 Dec;36(21):e143
references.pmid: 18940866
references.citation: Annu Rev Med. 2009;60:167-79
references.pmid: 19630570
references.citation: PLoS One. 2009;4(4):e5311
references.pmid: 19390579
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1553-8
references.pmid: 20080637
references.citation: Genome Res. 2008 Nov;18(11):1787-97
references.pmid: 18849523
references.citation: Cell. 2004 Mar 19;116(6):779-93
references.pmid: 15035981
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Nat Cell Biol. 2009 Mar;11(3):228-34
references.pmid: 19255566
references.citation: Oncogene. 2008 Sep 4;27(39):5204-13
references.pmid: 18504438
references.citation: PLoS One. 2009 Nov 16;4(11):e7850
references.pmid: 19924232