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Knockdown of PKCε Expression Inhibits Growth, Induces Apoptosis and Decreases Invasiveness of Human Glioma Cells Partially Through Stat3

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Abstract

Glioma is the most common primary central nervous system tumor. Despite considerable research effort, little progress has been made in the therapeutic treatment of this disease. Protein kinase Cε (PKCε), an important intracellular signaling molecule, modulates diverse cellular functions, including cell proliferation, apoptosis, invasion and differentiation. The aim of the study is to investigate whether knockdown of PKCε expression by RNA interference (RNAi) could affect the growth, apoptosis and invasion of human glioma cells, and the involvement of the signal transducer and activator of transcription 3 (Stat3) signaling pathway in these effects. Our data showed that knockdown of PKCε expression inhibited proliferation, induced apoptosis and decreased invasiveness of human glioma cell lines U251 and U87, as well as suppressed the growth of U87 cell-derived tumors in nude mice. Moreover, PKCε physically interacts with Stat3, and knockdown of PKCε expression attenuated Stat3Ser727 phosphorylation and B-cell lymphoma-extra large (Bcl-xL) expression in the two human glioma cell lines. These results support an important role for PKCε in glioma cell growth, apoptosis and invasion, and PKCε exerting its above effects at least in part through Stat3. Thus, PKCε has the potential to be an attractive therapeutic target for glioma therapy.

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Acknowledgments

This work was supported by the Innovation Program of Shanghai Municipal Education Commission (grant no. 12ZZ100), the Leading Academic Discipline Project of Shanghai Municipal Education Commission ‘Molecular Physiology’ (grant no. J50108), and the National Basic Research Program of China (grant no. 2010CB529806).

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  1. School of Life Sciences, Shanghai University, Number 99 Shangda Road, Shanghai, 200444, China

    Yaming Xu, Zhe Li, Can Zhang, Shiyun Zhang, Yonghua Ji & Fuxue Chen

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  1. Yaming Xu
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  2. Zhe Li
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  3. Can Zhang
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  4. Shiyun Zhang
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  5. Yonghua Ji
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Correspondence to Fuxue Chen.

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Xu, Y., Li, Z., Zhang, C. et al. Knockdown of PKCε Expression Inhibits Growth, Induces Apoptosis and Decreases Invasiveness of Human Glioma Cells Partially Through Stat3. J Mol Neurosci 55, 21–31 (2015). https://doi.org/10.1007/s12031-014-0341-4

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  • DOI: https://doi.org/10.1007/s12031-014-0341-4

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