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MYCN regulates oncogenic MicroRNAs in neuroblastoma
Author(s) -
Schulte Johannes H.,
Horn Sebastian,
Otto Tobias,
Samans Birgit,
Heukamp Lukas C.,
Eilers UrsulaChrista,
Krause Michael,
Astrahantseff Kathy,
KleinHitpass Ludger,
Buettner Reinhard,
Schramm Alexander,
Christiansen Holger,
Eilers Martin,
Eggert Angelika,
Berwanger Bernd
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23153
Subject(s) - neuroblastoma , microrna , biology , n myc , cancer research , downregulation and upregulation , microarray analysis techniques , oncogene , gene , messenger rna , regulation of gene expression , gene expression , microbiology and biotechnology , genetics , cell culture , cell cycle , ganglioneuroma
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. © 2007 Wiley‐Liss, Inc.