@article{30221ef8913a47db9887bcc67dcd1115,
title = "MicroRNA-182 promot es 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 mi{\~R}18{\~3}9{\~6}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.",
keywords = "Hsa-miR-182, Medulloblastoma, Metastatic dissemination, SHH pathway",
author = "Bai, {Alfa H.C.} and Till Milde and Marc Remke and Rolli, {Claudio G.} and Thomas Hielscher and Cho, {Yoon Jae} and Marcel Kool and Northcott, {Paul A.} and Manfred Jugold and Bazhin, {Alexandr V.} and Eichm{\"u}ller, {Stefan B.} and Kulozik, {Andreas E.} and Armin Pscherer and Axel Benner and Taylor, {Michael D.} and Pomeroy, {Scott L.} and Ralf Kemkemer and Olaf Witt and Andrey Korshunov and Peter Lichter and Pfister, {Stefan M.}",
note = "Funding Information: Acknowledgments We gratefully thank the patients and families for participating in this research. Jennifer Diemer and Anna Sch{\"o}ttler are acknowledged for excellent technical assistance. Support by the DKFZ Light Microscopy Facility is gratefully acknowledged. This study was supported by a grant from the Deutsche Kinderkrebsstif-tung and from the {\textquoteleft}{\textquoteleft}Tumorzentrum Heidelberg{\textquoteright}{\textquoteright} to S.M.P.; a {\textquoteleft}{\textquoteleft}Young Investigator Fellowship{\textquoteright}{\textquoteright} of the Medical Faculty of Heidelberg and financial support by the Eliteprogramme for Postdocs (Baden-W{\"u}rt-temberg Stiftung) to M.R.",
year = "2012",
month = apr,
doi = "10.1007/s00401-011-0924-x",
language = "English",
volume = "123",
pages = "529--538",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "4",
}