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    Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma

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    Publication date
    2014-01
    Author
    Ando, H.
    Natsume, A.
    Senga, T.
    Watanabe, R.
    Ito, I.
    Ohno, M.
    Iwami, K.
    Ohka, F.
    Motomura, K.
    Kinjo, S.
    Ito, M.
    Saito, K.
    Morgan, Richard
    Wakabayashi, T.
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    Keyword
    Meningioma; HOXA9; HXR9 peptide; Intracranial tumors
    Peer-Reviewed
    yes
    
    Metadata
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    Abstract
    Background Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX. Methods We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers. Results We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors. Conclusion There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease.
    URI
    http://hdl.handle.net/10454/10104
    Version
    No full-text in the repository
    Citation
    Ando H, Natsume A, Senga T, et al. (2014) Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma. Cancer Chemotherapy and Pharmacology. 73 (1): 53-60.
    Link to publisher’s version
    http://dx.doi.org/10.1007/s00280-013-2316-5
    Type
    Article
    Collections
    Life Sciences Publications

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