title: MicroRNA-182 promotes leptomeningeal spread of non-sonic hedgehog-medulloblastoma.
abstract: The contribution of microRNAs to the initiation, progression, and metastasis of medulloblastoma (MB) remains poorly understood. Metastatic dissemination at diagnosis is present in about 30% of MB patients, and is associated with a dismal prognosis. Using microRNA expression profiling, we demonstrate that the retinal miR-183-96-182 cluster on chromosome 7q32 is highly overexpressed in non-sonic hedgehog MBs (non-SHH-MBs). Expression of miR-182 and miR-183 is associated with cerebellar midline localization, and miR-182 is significantly overexpressed in metastatic MB as compared to non-metastatic tumors. Overexpression of miR-182 in non-SHH-MB increases and knockdown of miR-182 decreases cell migration in vitro. Xenografts overexpressing miR-182 invaded adjacent normal tissue and spread to the leptomeninges, phenotypically reminiscent of clinically highly aggressive large cell anaplastic MB. Hence, our study provides strong in vitro and in vivo evidence that miR-182 contributes to leptomeningeal metastatic dissemination in non-SHH-MB. We therefore reason that targeted inhibition of miR-182 may prevent leptomeningeal spread in patients with non-SHH-MB.
authors: Division of Molecular Genetics (B060), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Alfa H C
authors: AH
authors: Bai
authors: Till
authors: T
authors: Milde
authors: Marc
authors: M
authors: Remke
authors: Claudio G
authors: CG
authors: Rolli
authors: Thomas
authors: T
authors: Hielscher
authors: Yoon-Jae
authors: YJ
authors: Cho
authors: Marcel
authors: M
authors: Kool
authors: Paul A
authors: PA
authors: Northcott
authors: Manfred
authors: M
authors: Jugold
authors: Alexandr V
authors: AV
authors: Bazhin
authors: Stefan B
authors: SB
authors: Eichmüller
authors: Andreas E
authors: AE
authors: Kulozik
authors: Armin
authors: A
authors: Pscherer
authors: Axel
authors: A
authors: Benner
authors: Michael D
authors: MD
authors: Taylor
authors: Scott L
authors: SL
authors: Pomeroy
authors: Ralf
authors: R
authors: Kemkemer
authors: Olaf
authors: O
authors: Witt
authors: Andrey
authors: A
authors: Korshunov
authors: Peter
authors: P
authors: Lichter
authors: Stefan M
authors: SM
authors: Pfister
mesh_terms: D000293:Adolescent; D000818:Animals; D054443:Cell Migration Assays; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology*; D008577:Meningeal Neoplasms / Q000235:genetics / Q000556:secondary*; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D014183:Transplantation, Heterologous / Q000379:methods; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D053823:Hedgehog Proteins; C533449:MIRN183 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C509239:SHH protein, human; D051153:Wnt Proteins