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Loss of Diacylglycerol Kinase-Ζ Inhibits Cell Proliferation and Survival in Human Gliomas

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Abstract

Diacylglycerol kinases ζ (DGKζ) is a critical lipid kinase which is involved in phosphatidic acid (PA) generation via diacylglycerol (DAG) phosphorylation. DGKζ is highly expressed in central nervous system and essential for brain development. Studies have indicated that DGKζ is associated with colon cancer invasion and metastasis. However, the involvement of DGKζ in human glioma development remains elusive. Here, we explored the impact and possible mechanisms of DGKζ knockdown on the proliferation and survival of glioma cells. The relationship between DGKζ expression status and human glioma stages was explored in 111 specimens of human gliomas via immunohistochemistry technology. Then the impact of DGKζ on cell proliferation, cell cycle, survival, and colony formation ability was determined in U-87 MG glioma cell lines via lentiviral-mediated small interfering (shRNA) strategy. The influence of DGKζ knockdown on global gene expression in U-87 MGglioma cell lines was further analyzed by microarray platform to reveal the possible molecular mechanisms underlying DGKζ-mediated glioma development and progression. Immunohistochemistry analysis revealed that DGKζ expression is positively correlated with human gliomagrade. Lentiviral-mediated small interfering (shRNA) strategyefficiently reduced DGKζ expression and DGKζ knockdown impaired cell proliferation, inhibited colony formation ability, and induced cell cycle arrest and cell apoptosis in U-87 MG glioma cells. Finally, microarray analysis revealed that multiple cancer-associated pathways and oncogenes were regulated by DGKζ knockdown, which provides insights into underlying mechansims of DGKζ-associated glioma development and progression. Our results established the positive correlation between DGKζ expression and gliomagrade. Furthermore, DGKζ knockdown in human glioma cell lines U-87 MG impaired cell proliferation, inhibited colony formation ability, and induced cell cycle arrest and apoptosis which microarray analysis showed that DGKζ knockdown interrupted multiple oncogenes and cancer-associated pathways. Taken together, we provided confidential evidence for the causal role of DGKζ in glioma development and progression.

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Authors and Affiliations

  1. The General Hospital of PLA, Beijing, 100853, China

    Jinfu Diao

  2. Department of Neurosurgery, The Armed Police General Hospital, Beijing, 100039, China

    Jinfu Diao & Shanmin Zhao

  3. Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, Jiangsu, China

    Chunyong Wu

  4. Department of Pharmaceutics of Traditional Chinese Medicine, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, Jiangsu, China

    Junying Zhang

  5. Department of Neurosurgery, The First Affiliated Hospital of General Hospital of PLA, Beijing, 100853, China

    Jialin Liu & Zhiwen Zhang

  6. Department of Pathology, The Armed Police General Hospital, Beijing, 100039, China

    Xinwu Zhang

  7. The People’s Hospital of Xinglong County, Hebei, 067399, China

    Pengcheng Hao

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  1. Jinfu Diao
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Correspondence to Zhiwen Zhang.

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Co-first authors: Jinfu Diao and Chunyong Wu

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Diao, J., Wu, C., Zhang, J. et al. Loss of Diacylglycerol Kinase-Ζ Inhibits Cell Proliferation and Survival in Human Gliomas. Mol Neurobiol 53, 5425–5435 (2016). https://doi.org/10.1007/s12035-015-9419-4

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  • DOI: https://doi.org/10.1007/s12035-015-9419-4

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