Ye Shan-Ping, Yu Hong-Xin, Lu Wei-Jie, Wang Jun-Fu, Li Tai-Yuan, Shi Jun, Cheng Xiao-Ye
Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, Jiangxi Province 330006, China.
Department of Hematology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, Jiangxi Province 330006, China.
Int J Genomics. 2023 Aug 8;2023:9731675. doi: 10.1155/2023/9731675. eCollection 2023.
Abnormal stratifin (SFN) expression is closely related to the progression of several human cancers, but the potential roles of SFN in hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that SFN was upregulated in HCC cell lines and tissues and was positively associated with tumor size, poor differentiation, Tumor Node Metastasis (TNM) stage, and vascular invasion. In addition, high expression levels of SFN were associated with poor overall survival and disease-free survival. Biologically, downregulation of SFN suppressed tumor cell proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration in vitro and tumor growth in vivo. However, overexpression of SFN promoted cell proliferation, EMT, invasion, and migration in vitro and tumor growth in vivo. Mechanistically, overexpression of SFN activated the Wnt/-catenin pathway by promoting Glycogen synthase kinase-3 beta (GSK-3) phosphorylation, decreasing -catenin phosphorylation, promoting -catenin transport into the nucleus, and enhancing the expression of c-Myc, whereas depletion of SFN inhibited the Wnt/-catenin pathway. In addition, TOPFlash/FOPFlash reporter assays showed that overexpression or downregulation of SFN obviously increased or decreased, respectively, the activity of the Wnt/-catenin pathway. Our results indicated that SFN plays an important role in HCC, possibly providing a prognostic factor and therapeutic target for HCC.
异常的14-3-3σ（SFN）表达与多种人类癌症的进展密切相关，但SFN在肝细胞癌（HCC）中的潜在作用仍不清楚。在本研究中，我们发现SFN在肝癌细胞系和组织中上调，并且与肿瘤大小、低分化、肿瘤淋巴结转移（TNM）分期及血管侵犯呈正相关。此外，SFN高表达与总体生存期和无病生存期较差相关。生物学上，SFN下调抑制体外肿瘤细胞增殖、上皮-间质转化（EMT）、侵袭及迁移以及体内肿瘤生长。然而，SFN过表达促进体外细胞增殖、EMT、侵袭及迁移以及体内肿瘤生长。机制上，SFN过表达通过促进糖原合酶激酶-3β（GSK-3）磷酸化、降低β-连环蛋白磷酸化、促进β-连环蛋白转运入核以及增强c-Myc表达激活Wnt/β-连环蛋白通路，而SFN缺失则抑制Wnt/β-连环蛋白通路。此外，TOPFlash/FOPFlash报告基因检测显示，SFN过表达或下调分别明显增加或降低Wnt/β-连环蛋白通路的活性。我们的结果表明，SFN在肝癌中起重要作用，可能为肝癌提供一个预后因素和治疗靶点。
