Int J Biol Sci 2019; 15(9):1872-1881. doi:10.7150/ijbs.35193 This issue

Research Paper

DGKζ Plays Crucial Roles in the Proliferation and Tumorigenicity of Human glioblastoma

Xuefeng Gu1,2,6,†, Guoqing Wan1,6,†, Nianhong Chen1,6,†, Jinhong Li3, Bing Chen4, Yeling Tang1, Wangxian Gu1, Cuiting Jin1, Jihong Meng1, Peng Zhang5, Li Liu2, Zhifang Yang2✉, Changlian Lu1,6✉

1. Collaborative Research Center, Shanghai University of Medicine & Health Sciences, Shanghai, PR China
2. College of Fundamental Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, PR China
3. Department of Neurosurgery, Jiangmen Central Hospital, Jiangmen, Guangdong, PR China
4. Department of Neurosurgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, PR China
5. College of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, PR China
6. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, PR China
† contributed equally to this work

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Citation:
Gu X, Wan G, Chen N, Li J, Chen B, Tang Y, Gu W, Jin C, Meng J, Zhang P, Liu L, Yang Z, Lu C. DGKζ Plays Crucial Roles in the Proliferation and Tumorigenicity of Human glioblastoma. Int J Biol Sci 2019; 15(9):1872-1881. doi:10.7150/ijbs.35193. Available from https://www.ijbs.com/v15p1872.htm

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Abstract

Graphic abstract

Glioblastoma is one of the most malignant brain cancers in adults, and it is a fatal disease because of its untimely pathogenetic location detection, infiltrative growth, and unfavorable prognosis. Unfortunately, multimodal treatment with maximal safe resection, chemotherapy and radiation has not increased the survival rate of patients with glioblastoma. Gene- and molecular-targeted therapy is considered to be a promising anticancer strategy for glioblastoma. The identification of novel potential targets in glioblastoma is of high importance. In this study, we found that both the mRNA and protein levels of diacylglycerol kinase ζ (DGKζ) were significantly higher in glioblastoma tissues than in precancerous lesions. The silencing of DGKζ by lentivirus-delivered shRNA reduced glioblastoma cell proliferation and induced G0/G1 phase arrest. Moreover, knockdown of DGKζ expression in U251 cells markedly reduced in vitro colony formation and in vivo tumorigenic capability. Further study showed that DGKζ inhibition resulted in decreases in cyclin D1, p-AKT and p-mTOR. Moreover, the rescue or overexpression of DGKζ in glioblastoma cells demonstrated the oncogenic function of DGKζ. In conclusion, these studies suggest that the suppression of DGKζ may inhibit the tumor growth of glioblastoma cells with high DGKζ expression. Thus, DGKζ might be a potential therapeutic target in malignant glioblastoma.

Keywords: Diacylglycerol kinase zeta (DGKζ), glioblastoma, phosphorylation, cell proliferation, tumorigenicity