Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma (Retracted article. See vol. 55, pg. 138, 2021)
Elevated Expression of Zinc Finger Protein 703 Promotes Cell Proliferation and Metastasis through PI3K/AKT/GSK-3β Signalling in Oral Squamous Cell Carcinoma (Retracted article. See vol. 55, pg. 138, 2021)
复制标题
口腔鳞状细胞癌中锌指蛋白 703 的表达升高通过 PI3K/AKT/GSK-3β 信号传导促进细胞增殖和转移
DOI：
10.1159/000485360
复制
发表时间：
2017-01-01
影响因子：
--
通讯作者：
Huo, Shaofen
中科院分区：
文献类型：
--
作者：
Wang, Hao;Deng, Xubin;Huo, Shaofen
背景/目的：锌指蛋白703（ZNF703）最初被鉴定为人类乳腺癌中的一种新型致癌基因，是锌指转录因子NET/NlZ家族的成员。已知ZNF703的过度表达与多种人类癌症相关，但ZNF703在口腔鳞状细胞癌（OSCC）中的作用和分子机制尚不清楚。
方法：通过实时定量聚合酶链反应（qRT - PCR）和免疫组织化学（IHC）检测OSCC组织和非癌组织中ZNF703的表达水平。利用CCK8检测、集落形成检测、细胞周期分析、迁移和侵袭检测、伤口愈合检测、蛋白质印迹法以及裸鼠异种移植实验，在体外和体内探究ZNF703的分子机制及其对细胞生长和转移的影响。
结果：在本研究中，发现ZNF703在OSCC组织中的mRNA和蛋白质水平均高于正常组织，并且其表达水平与OSCC患者的总体生存率密切相关。在OSCC细胞中沉默ZNF703基因在体外和体内均显著抑制细胞生长和转移。相反，在OSCC细胞中过表达ZNF703在体外促进癌症生长和转移。从机制上讲，ZNF703激活PI3K/AKT/GSK - 3β信号通路及其下游效应因子，从而调节细胞周期和上皮 - 间质转化（EMT）。此外，LY294002（一种PI3K特异性抑制剂）和MK2206（一种Akt特异性抑制剂）可逆转ZNF703对细胞增殖和转移的促进作用。
结论：结果表明，ZNF703通过PI3K/Akt/GSK - 3β信号通路促进OSCC中的细胞生长和转移，它可能是治疗OSCC患者的一个有前景的靶点。（C）2017作者，由巴塞尔S.Karger AG出版
Background/Aims: Zinc finger protein 703 (ZNF703), initially identified as a novel oncogene in human breast cancer, is a member of the NET/NlZ family of zinc finger transcription factors. It is recognized that the overexpression of ZNF703 is associated with various types of human cancers, but the role and molecular mechanism of ZNF703 in oral squamous cell carcinoma (OSCC) are unknown. Methods: ZNF703 expression levels were examined in OSCC tissues and non-cancerous tissues by qRT-PCR and immunohistochemistry (IHC). The molecular mechanisms of ZNF703 and its effects on cell growth and metastasis were explored in vitro and in vivo using the CCK8 assay, colony formation assay, cell cycle analysis, migration and invasion assays, wound-healing assay, western blotting and xenograft experiments in nude mice. Results: In this study, ZNF703 was found to be upregulated in OSCC tissues compared to that in normal tissues at both mRNA and protein levels, and its expression level was closely correlated with the overall survival of patients with OSCC. Silencing of the ZNF703 gene in OSCC cells significantly inhibited cell growth and metastasis in vitro and in vivo. Conversely, the overexpression of ZNF703 in OSCC cells promoted cancer growth and metastasis in vitro. Mechanistically, ZNF703 activated the PI3K/AKT/GSK-3β signalling pathway and its downstream effectors, thus regulating the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, the promotive effects of ZNF703 on cellular proliferation and metastasis could be rescued by LY294002 (a PI3K-specific inhibitor) and MK2206 (an Akt-specific inhibitor). Conclusion: The results show that ZNF703 promotes cell growth and metastasis through PI3K/Akt/GSK-3β signalling in OSCC and that it may be a promising target in the treatment of patients with OSCC.