MYCN regulates oncogenic MicroRNAs in neuroblastoma.
MYCN amplification is a common feature of aggressive tumour biology in neuroblastoma. The MYCN transcription factor has been demonstrated to induce or repress expression of numerous genes. MicroRNAs (miRNA) are a recently discovered class of short RNAs that repress translation and promote mRNA degradation by sequence-specific interaction with mRNA. Here, we sought to analyse the role of MYCN in regulation of miRNA expression. Using a miRNA microarray containing 384 different miRNAs and a set of 160 miRNA real-time PCR assays to validate the microarray results, 7 miRNAs were identified that are induced by MYCN in vitro and are upregulated in primary neuroblastomas with MYCN amplification. Three of the seven miRNAs belong to the miR-106a and miR-17 clusters, which have previously been shown to be regulated by c-Myc. The miR-17-92 polycistron also acts as an oncogene in haematopoietic progenitor cells. We show here that miR-221 is also induced by MYCN in neuroblastoma. Previous studies have reported miR-221 to be overexpressed in several other cancer entities, but its regulation has never before been associated with Myc. We present evidence of miRNA dysregulation in neuroblastoma. Additionally, we report miRNA induction to be a new mechanism of gene expression downregulation by MYCN.
Schulte
Johannes H
JH
Department of Pediatric Oncology and Haematology, University Children's Hospital Essen, Essen, Germany. johannes.schulte@uk-essen.de
Horn
Sebastian
S
Otto
Tobias
T
Samans
Birgit
B
Heukamp
Lukas C
LC
Eilers
Ursula-Christa
UC
Krause
Michael
M
Astrahantseff
Kathy
K
Klein-Hitpass
Ludger
L
Buettner
Reinhard
R
Schramm
Alexander
A
Christiansen
Holger
H
Eilers
Martin
M
Eggert
Angelika
A
Berwanger
Bernd
B
D015153:Blotting, Western; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D046228:Microarray Analysis; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000494:pharmacology*; D015513:Oncogene Proteins / Q000494:pharmacology*; D009857:Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction
C459801:MYCN protein, human; D035683:MicroRNAs; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins