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  • Interaction Between MELK and EZH2 Regulates Medulloblastoma Cancer Stem-like Cells Proliferation

    Final Number:
    228

    Authors:
    Hailong Liu; Qianwen Sun; Chunjiang Yu; Chunyu Gu; Hongwei Zhang

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2017 Annual Meeting

    Introduction: Medulloblastoma (MB) is the most common malignant brain tumor in children. Although accumulated research suggests that cancer stem-like cells may play a key role in medullolastoma tumorigenesis, the molecular mechanisms of proliferation still remain elusive and further investigation can provide a novel application for therapeutic target in MB patients.

    Methods: The expression of MELK and EZH2 was detected by tissue microarray analysis with 88 MBs and its association with prognosis was identified. Co-location of MELK and EZH2 in MB CSCs and tissues was studied by using confocal and immunostaining. Immunoblotting analysis following co-immunoprecipitation was performed to check the interaction between MELK and EZH2. Through the loss-of-function study by siRNA, CSCs-drived tumor growth was detected. Then we studied the targeted treatment of MB with MELK and EZH2 inhibitor in vivo to confirm the molecular basis of MELK and EZH2.

    Results: MELK and EZH2 co-located in the nuclei of MB CSCs and MB with extensive nodularity and large cell/anaplastic differed the staining levels as measured using microarray analysis when compared with the other two subgroups. The proportion of MELK positive staining cells was the potential indicator for the survival. MELK bound and phosphorylated EZH2 and its methylation was induced by EZH2 in MB, which regulated the proliferation of CSCs. MELK and EZH2 depletion by siRNA or treatment of inhibitors attenuated the MB CSCs-derived tumor growth in vivo.

    Conclusions: Interaction between MELK and EZH2 is essential for MB CSCs-drived tumor proliferation, thereby identifying a potential therapeutic strategy for MB patients.

    Patient Care: The research confirmed the interaction between MELK and EZH2 proteins in MB and highlighted the therapeutic effects after both proteins were inhibited.

    Learning Objectives: To identify the important role of the interaction between MELK and EZH2 in medulloblastoma proliferation and then confirm a new advancing therapeutic strategy for MB.

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