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Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells

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Abstract

DEP domain containing 1 (DEPDC1) is a novel oncoantigen expressed in cancer cells, which presents oncogenic activity and high immunogenicity. Although DEPDC1 has been predicted to be a useful antigen for the development of a cancer vaccine, its pathophysiological roles in glioma have not been investigated. Here, we analyzed the expression and function of DEPDC1 in malignant glioma. DEPDC1 expression in glioma cell lines, glioma tissues, and brain tumor initiating cells (BTICs) was assessed by western blot and quantitative polymerase chain reaction (PCR). The effect of DEPDC1 downregulation on cell growth and nuclear factor kappa B (NFκB) signaling in glioma cells was investigated. Overall survival was assessed in mouse glioma models using human glioma cells and induced mouse brain tumor stem cells (imBTSCs) to determine the effect of DEPDC1 suppression in vivo. DEPDC1 expression was increased in glioma cell lines, tissues, and BTICs. Suppression of endogenous DEPDC1 expression by small interfering RNA (siRNA) inhibited glioma cell viability and induced apoptosis through NFκB signaling. In mouse glioma models using human glioma cells and imBTSCs, downregulation of DEPDC1 expression prolonged overall survival. These results suggest that DEPDC1 represents a target molecule for the treatment of glioma.

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Acknowledgements

We thank Ms. Yuko Aikawa, Tomoko Muraki, and Naoko Tsuzaki (Department of Neurosurgery, Keio University School of Medicine) for technical assistance.

Funding

This research was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (B), Grant Number 15K19979.

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Authors and Affiliations

  1. Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan

    Ryogo Kikuchi, Kazunari Yoshida & Masahiro Toda

  2. Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan

    Oltea Sampetrean & Hideyuki Saya

Authors
  1. Ryogo Kikuchi
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  2. Oltea Sampetrean
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  3. Hideyuki Saya
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  4. Kazunari Yoshida
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  5. Masahiro Toda
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Correspondence to Masahiro Toda.

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Kikuchi, R., Sampetrean, O., Saya, H. et al. Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells. J Neurooncol 133, 297–307 (2017). https://doi.org/10.1007/s11060-017-2457-1

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  • DOI: https://doi.org/10.1007/s11060-017-2457-1

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