Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Thoracic surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer Med. 2019 Feb;8(2):783-794. doi: 10.1002/cam4.1950. Epub 2019 Jan 18.
14-3-3ζ has been reported to function as critical regulators of diverse cellular responses. However, the role of 14-3-3ζ in gliomas progression remains largely unknown. The expression level of 14-3-3ζ and Snail was detected by Western blot analysis and quantitative polymerase chain reaction in different grades of human gliomas. The effect of 14-3-3ζ on gliomas progression was measured using cell migration and invasion assay, the colony formation experiment, and CCK-8 assay. The effect of 14-3-3ζ on PI3K/AKT/Snail signaling protein expression levels was tested by Western blotting. Firstly, 14-3-3ζ was often up-regulated in high-grade gliomas relative to low-grade gliomas, and this overexpression was significantly related to tumor size, Karnofsky Performance Scale score and weaker disease-free survival. Secondly, the overexpression of 14-3-3ζ promoted gliomas cells proliferation, migration, and invasion. Conversely, the knockdown of 14-3-3ζ suppressed gliomas cells proliferation, migration, and invasion. Furthermore, subsequent mechanistic studies showed that 14-3-3ζ could activate PI3K/AKT/Snail signaling pathway to facilitate gliomas cells proliferation, migration, and invasion. This study shows that the overexpression of 14-3-3ζ can promote remarkably gliomas cells proliferation, migration, and invasion by regulating the Snail protein expression through activating PI3K/AKT signaling, and it may serve as a potential prognostic marker and therapeutic target for gliomas.
14-3-3ζ 已被报道作为多种细胞反应的关键调节因子发挥作用。然而，14-3-3ζ 在神经胶质瘤进展中的作用在很大程度上尚不清楚。通过 Western blot 分析和定量聚合酶链反应检测不同级别人类神经胶质瘤中 14-3-3ζ 和 Snail 的表达水平。通过细胞迁移和侵袭测定、集落形成实验和 CCK-8 测定来测量 14-3-3ζ 对神经胶质瘤进展的影响。通过 Western blot 检测 14-3-3ζ 对 PI3K/AKT/Snail 信号蛋白表达水平的影响。首先，与低级别神经胶质瘤相比，14-3-3ζ 通常在高级别神经胶质瘤中上调，这种过表达与肿瘤大小、卡诺夫斯基表现量表评分和较弱的无病生存率显著相关。其次，14-3-3ζ 的过表达促进神经胶质瘤细胞的增殖、迁移和侵袭。相反，14-3-3ζ 的敲低抑制了神经胶质瘤细胞的增殖、迁移和侵袭。此外，随后的机制研究表明，14-3-3ζ 可以通过激活 PI3K/AKT/Snail 信号通路来促进神经胶质瘤细胞的增殖、迁移和侵袭，从而促进神经胶质瘤细胞的增殖、迁移和侵袭。本研究表明，通过激活 PI3K/AKT 信号来调节 Snail 蛋白表达，14-3-3ζ 的过表达可以显著促进神经胶质瘤细胞的增殖、迁移和侵袭，它可能成为神经胶质瘤的一个有潜力的预后标志物和治疗靶点。
