MicroRNA-182 promot es leptomeningeal spread of non-sonic hedgehog-medulloblastoma

Alfa H.C. Bai, Till Milde, Marc Remke, Claudio G. Rolli, Thomas Hielscher, Yoon-Jae Cho, Marcel Kool, Paul A. Northcott, Manfred Jugold, Alexandr V. Bazhin, Stefan B. Eichmüller, Andreas E. Kulozik, Armin Pscherer, Axel Benner, Michael D. Taylor, Scott L. Pomeroy, Ralf Kemkemer, Olaf Witt, Andrey Korshunov, Peter LichterStefan M. Pfister

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 miR̃183̃96̃182 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.

Original languageEnglish (US)
Pages (from-to)529-538
Number of pages10
JournalActa Neuropathologica
Volume123
Issue number4
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

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Medulloblastoma
MicroRNAs
Heterografts
Cell Movement
Chromosomes
Neoplasm Metastasis
Neoplasms

Keywords

  • Hsa-miR-182
  • Medulloblastoma
  • Metastatic dissemination
  • SHH pathway

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Bai, A. H. C., Milde, T., Remke, M., Rolli, C. G., Hielscher, T., Cho, Y-J., ... Pfister, S. M. (2012). MicroRNA-182 promot es leptomeningeal spread of non-sonic hedgehog-medulloblastoma. Acta Neuropathologica, 123(4), 529-538. https://doi.org/10.1007/s00401-011-0924-x

MicroRNA-182 promot es leptomeningeal spread of non-sonic hedgehog-medulloblastoma. / Bai, Alfa H.C.; Milde, Till; Remke, Marc; Rolli, Claudio G.; Hielscher, Thomas; Cho, Yoon-Jae; Kool, Marcel; Northcott, Paul A.; Jugold, Manfred; Bazhin, Alexandr V.; Eichmüller, Stefan B.; Kulozik, Andreas E.; Pscherer, Armin; Benner, Axel; Taylor, Michael D.; Pomeroy, Scott L.; Kemkemer, Ralf; Witt, Olaf; Korshunov, Andrey; Lichter, Peter; Pfister, Stefan M.

In: Acta Neuropathologica, Vol. 123, No. 4, 01.04.2012, p. 529-538.

Research output: Contribution to journalArticle

Bai, AHC, Milde, T, Remke, M, Rolli, CG, Hielscher, T, Cho, Y-J, Kool, M, Northcott, PA, Jugold, M, Bazhin, AV, Eichmüller, SB, Kulozik, AE, Pscherer, A, Benner, A, Taylor, MD, Pomeroy, SL, Kemkemer, R, Witt, O, Korshunov, A, Lichter, P & Pfister, SM 2012, 'MicroRNA-182 promot es leptomeningeal spread of non-sonic hedgehog-medulloblastoma', Acta Neuropathologica, vol. 123, no. 4, pp. 529-538. https://doi.org/10.1007/s00401-011-0924-x
Bai, Alfa H.C. ; Milde, Till ; Remke, Marc ; Rolli, Claudio G. ; Hielscher, Thomas ; Cho, Yoon-Jae ; Kool, Marcel ; Northcott, Paul A. ; Jugold, Manfred ; Bazhin, Alexandr V. ; Eichmüller, Stefan B. ; Kulozik, Andreas E. ; Pscherer, Armin ; Benner, Axel ; Taylor, Michael D. ; Pomeroy, Scott L. ; Kemkemer, Ralf ; Witt, Olaf ; Korshunov, Andrey ; Lichter, Peter ; Pfister, Stefan M. / MicroRNA-182 promot es leptomeningeal spread of non-sonic hedgehog-medulloblastoma. In: Acta Neuropathologica. 2012 ; Vol. 123, No. 4. pp. 529-538.
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AU - Bai, Alfa H.C.

AU - Milde, Till

AU - Remke, Marc

AU - Rolli, Claudio G.

AU - Hielscher, Thomas

AU - Cho, Yoon-Jae

AU - Kool, Marcel

AU - Northcott, Paul A.

AU - Jugold, Manfred

AU - Bazhin, Alexandr V.

AU - Eichmüller, Stefan B.

AU - Kulozik, Andreas E.

AU - Pscherer, Armin

AU - Benner, Axel

AU - Taylor, Michael D.

AU - Pomeroy, Scott L.

AU - Kemkemer, Ralf

AU - Witt, Olaf

AU - Korshunov, Andrey

AU - Lichter, Peter

AU - Pfister, Stefan M.

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N2 - 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 miR̃183̃96̃182 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.

AB - 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 miR̃183̃96̃182 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.

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