DGKζ Plays Crucial Roles in the Proliferation and Tumorigenicity of Human glioblastoma
| Autor: | Li Liu, Changlian Lu, Peng Zhang, Jihong Meng, Yeling Tang, Wangxian Gu, Zhifang Yang, Xuefeng Gu, Guoqing Wan, Cuiting Jin, Jinhong Li, Nian-Hong Chen, Bing Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Diacylglycerol Kinase Blotting Western Apoptosis Biology Applied Microbiology and Biotechnology Small hairpin RNA 03 medical and health sciences Cyclin D1 In vivo Cell Line Tumor Animals Humans Gene silencing Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Diacylglycerol kinase Diacylglycerol kinase zeta (DGKζ) 0303 health sciences Gene knockdown Brain Neoplasms phosphorylation Cell growth Cell Cycle glioblastoma Glioma Cell Biology Middle Aged Flow Cytometry Immunohistochemistry nervous system diseases Gene Expression Regulation Neoplastic cell proliferation Cancer research tumorigenicity Phosphorylation Female Research Paper Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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