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miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma cell migration and tumor growth in vivo

Oncogene volume 34, pages 1790–1798 (2015)Cite this article

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Abstract

miR-200a has been implicated in the pathogenesis of meningiomas, one of the most common central nervous system tumors in humans. To identify how miR-200a contributes to meningioma pathogenesis at the molecular level, we used a comparative protein profiling approach using Gel-nanoLC-MS/MS and identified approximately 130 dysregulated proteins in miR-200a-overexpressing meningioma cells. Following the bioinformatic analysis to identify potential genes targeted by miR-200a, we focused on the non-muscle heavy chain IIb (NMHCIIb), and showed that miR-200a directly targeted NMHCIIb. Considering the key roles of NMHCIIb in cell division and cell migration, we aimed to identify whether miR-200a regulated these processes through NMHCIIb. We found that NMHCIIb overexpression partially rescued miR-200a-mediated inhibition of cell migration, as well as cell growth in vitro and in vivo. Moreover, siRNA-mediated silencing of NMHCIIb expression resulted in a similar migration phenotype in these cells and inhibited meningioma tumor growth in mice. Taken together, these results suggest that NMHCIIb might serve as a novel therapeutic target in meningiomas.

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Acknowledgements

Support for this work was provided, in part, by Forschungsgesellschaft for Brain Tumors (to OS, NS), EU-FP7-PEOPLE-2011-CIG (to OS) and Association for Conduct of Scientific Research in the Field of Neonatology and Pediatric Intensive Care: ‘Unser Kind’ (to OS). We thank Dr Marianne F James for providing us with AC030 cells.

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Authors and Affiliations

  1. Department of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    O Senol

  2. Department of Medical Oncology, OncoProteomics Laboratory, VU University Medical Center, Amsterdam, The Netherlands

    T B M Schaaij-Visser, T V Pham, S R Piersma & C R Jimenez

  3. Department of Pediatrics, Molecular Neuro-Oncology Research Unit, Medical University of Vienna, Vienna, Austria

    E P Erkan, N Saydam, I Slavc & O Saydam

  4. Department of Neurosurgery, Medical University of Vienna, Vienna, Austria

    C Dorfer & E Knosp

  5. Experimental Therapeutics and Molecular Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    G Lewandrowski & B Tannous

  6. Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands

    S M Peerdeman

  7. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    T Ströbel

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  1. O Senol
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Correspondence to O Saydam.

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Senol, O., Schaaij-Visser, T., Erkan, E. et al. miR-200a-mediated suppression of non-muscle heavy chain IIb inhibits meningioma cell migration and tumor growth in vivo. Oncogene 34, 1790–1798 (2015). https://doi.org/10.1038/onc.2014.120

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