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Down-regulation of 14-3-3zeta reduces proliferation and increases apoptosis in human glioblastoma

Cancer Gene Therapy volume 27, pages 399–411 (2020)Cite this article

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Abstract

Many efforts have been taken to develop molecule target for cancer therapy. 14-3-3zeta protein has emerged as a critical regulator of diverse cellular pathways in multiple cancers. Furthermore, 14-3-3zeta expression was elevated and a predictor of poor prognosis in glioblastoma. However, there is no information to evaluate the potential effects of 14-3-3zeta RNAi in glioblastoma. The relationship between 14-3-3zeta expression and cell proliferation and apoptosis was tested in primary glioblastoma samples. Through an RNAi approach using human glioblastoma cells as a model system, we demonstrated the role of 14-3-3zeta in glioblastoma proliferation, apoptosis, invasion and tumor growth. The expression of 14-3-3zeta in glioblastoma stem cells was also investigated by immunostaining. The apoptosis was significantly higher in 14-3-3zeta-negative group than in positive group. 14-3-3zeta immunoreactivity score was negatively correlated with the apoptosis, and positively with proliferation in human specimens. 14-3-3zeta RNAi reduced cell proliferation, induced apoptosis, decreased the invasive capability and colony-formation, and impaired the growth of glioblastoma xenografts in nude mice. Moreover, 14-3-3zeta was positively expressed in glioblastoma stem cells. Our data highlight the importance of 14-3-3zeta in glioblastoma and identify 14-3-3zeta as a potential molecular target for glioblastoma treatment.

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Acknowledgements

The authors gratefully acknowledge Mauting Lin (Cancer Research Institute, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco) for his helpful communication and Bo Wang’s (Department of Epidemiology, School of Military Preventive Medicine in our university) help in statistical analysis. The authors thank Jingrong Hu (Department of Immune in our university) for assistance in flow cytometry and Wanjuan Yang for the preparation of material for this research.

Funding

Supported by the National Natural Science Foundation of China (Nos. 39970752, 81472357, and 81072083) and Scientific and Technological Project of ShaanXi Province (No. 2008K09-09).

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  1. These authors contributed equally: Xiaoliang Yang, Weidong Cao

Authors and Affiliations

  1. Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University, #127, Changle Western Road, Xi’an, 710032, Shaanxi Province, People’s Republic of China

    Xiaoliang Yang, Weidong Cao, Xiang Zhang & Wei Zhang

  2. Department of Neurosurgery, Third Hospital of People’s Liberation Army, #45, Dongfeng Road, Baoji, 721004, Shaanxi Province, People’s Republic of China

    Xiaoliang Yang & Xiaofeng Wang

  3. Department of Neurosurgery, The Sixth Medical Centre, Chinese PLA (People’s Liberation Army) General Hospital, #6, Fucheng Road, Haidian District, Beijing, 100048, People’s Republic of China

    Weidong Cao

  4. Department of Pharmacology and Winship Cancer Institute, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA

    Zenggang Li & Haian Fu

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Yang, X., Cao, W., Wang, X. et al. Down-regulation of 14-3-3zeta reduces proliferation and increases apoptosis in human glioblastoma. Cancer Gene Ther 27, 399–411 (2020). https://doi.org/10.1038/s41417-019-0097-7

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