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miRNA-145 is downregulated in atypical and anaplastic meningiomas and negatively regulates motility and proliferation of meningioma cells

Oncogene volume 32, pages 4712–4720 (2013)Cite this article

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Abstract

Meningiomas are frequent, mostly benign intracranial or spinal tumors. A small subset of meningiomas is characterized by histological features of atypia or anaplasia that are associated with more aggressive biological behavior resulting in increased morbidity and mortality. Infiltration into the adjacent brain tissue is a major factor linked to higher recurrence rates. The molecular mechanisms of progression, including brain invasion are still poorly understood. We have studied the role of micro-RNA 145 (miR-145) in meningiomas and detected significantly reduced miR-145 expression in atypical and anaplastic tumors as compared with benign meningiomas. Overexpression of miR-145 in IOMM-Lee meningioma cells resulted in reduced proliferation, increased sensitivity to apoptosis, reduced anchorage-independent growth and reduction of orthotopic tumor growth in nude mice as compared with control cells. Moreover, meningioma cells with high miR-145 levels had impaired migratory and invasive potential in vitro and in vivo. PCR-array studies of miR145-overexpressing cells suggested that collagen type V alpha (COL5A1) expression is downregulated by miR-145 overexpression. Accordingly, COL5A1 expression was significantly upregulated in atypical and anaplastic meningiomas. Collectively, our data indicate an important anti-migratory and anti-proliferative function of miR-145 in meningiomas.

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Acknowledgements

The skillful technical work of Ines Schellhase, Ines Meyer and Sandra Hartmann is highly appreciated. We thank Professor Till Acker (University of Giessen) for help with the morphometric quantification of tumor infiltration in mice and Grit Werner for her help with MR imaging. The work was supported by the Wilhelm Sander-Stiftung (grant #2010.017.1).

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Author notes

  1. N Kliese and P Gobrecht: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Neuropathology, Otto-von-Guericke University, Magdeburg, Germany

    N Kliese, P Gobrecht, D Pachow, N Andrae, A Wilisch-Neumann, E Kirches & C Mawrin

  2. Project Group Neuropharmacology, Leibniz-Institute for Neurobiology, Magdeburg, Germany

    M Riek-Burchardt

  3. Laboratory for Non-Invasive Animal Imaging, Leibniz-Institute for Neurobiology, Magdeburg, Germany

    F Angenstein

  4. Department of Neuropathology, Heinrich Heine University, Düsseldorf, Germany

    G Reifenberger

  5. Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany

    M J Riemenschneider

  6. Department of Human Genetics, Saarland University, Homburg/Saar, Germany

    E Meese

  7. Department of Dermatology, University of Heidelberg, Heidelberg, Germany

    D Panayotova-Dimitrova

  8. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA

    D H Gutmann

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  1. N Kliese
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Correspondence to C Mawrin.

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Kliese, N., Gobrecht, P., Pachow, D. et al. miRNA-145 is downregulated in atypical and anaplastic meningiomas and negatively regulates motility and proliferation of meningioma cells. Oncogene 32, 4712–4720 (2013). https://doi.org/10.1038/onc.2012.468

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