title: MYCN regulates oncogenic MicroRNAs in neuroblastoma.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology and Haematology, University Children's Hospital Essen, Essen, Germany. johannes.schulte@uk-essen.de
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.forename: Sebastian
authors.initials: S
authors.lastname: Horn
authors.forename: Tobias
authors.initials: T
authors.lastname: Otto
authors.forename: Birgit
authors.initials: B
authors.lastname: Samans
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.forename: Ursula-Christa
authors.initials: UC
authors.lastname: Eilers
authors.forename: Michael
authors.initials: M
authors.lastname: Krause
authors.forename: Kathy
authors.initials: K
authors.lastname: Astrahantseff
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.forename: Holger
authors.initials: H
authors.lastname: Christiansen
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.forename: Bernd
authors.initials: B
authors.lastname: Berwanger
mesh_terms: 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
chemical_list: C459801:MYCN protein, human; D035683:MicroRNAs; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins