Liu Yuzhen, Qiao Yanchun, Zhang Hangyu, Li Wentong, Zheng Jie
Department of Pathology, Weifang Medical University, Shandong, China.
Department of Pathology, Affiliated Hospital of Weifang Medical University, Shandong, China.
J Cell Biochem. 2019 Oct;120(10):18142-18151. doi: 10.1002/jcb.29118. Epub 2019 May 29.
Wnt7a is a member of the Wnt family and has been reported to be involved in the carcinogenesis and progression of many types of human cancer. However, little is known about Wnt7a expression and function in gastric cancer (GC). In the present study, Wnt7a expression in GC tissues and cells was investigated, the correlation between Wnt7a expression and the prognosis was also examined. The effects of Wnt7a on proliferation, invasion, and metastasis were evaluated in vitro and in vivo. Furthermore, the expression of epithelial-mesenchymal transition (EMT) markers and hypermethylation of the Wnt7a promoter were both detected. Wnt7a was downregulated in GC and its expression was associated with poor prognosis of patients with GC. Moreover, upregulation of Wnt7a significantly suppressed the growth, invasion, and metastasis abilities of GC cells in vitro and in vivo. Mechanistically, Wnt7a was found to inhibit EMT process of GC cells. In addition, the reducing expression of Wnt7a was due to methylation of 5'-CpG island within the promoter. Furthermore, the tumor suppressor role of Wnt7a is independent of canonical Wnt/β-catenin signaling in GC cells. In conclusion, our findings demonstrated that Wnt7a could be used as a potential diagnostic marker and target for GC management.
Wnt7a是Wnt家族的一员，据报道它参与多种人类癌症的发生和发展。然而，关于Wnt7a在胃癌（GC）中的表达和功能却知之甚少。在本研究中，我们调查了Wnt7a在GC组织和细胞中的表达情况，并检测了Wnt7a表达与预后之间的相关性。我们在体外和体内评估了Wnt7a对增殖、侵袭和转移的影响。此外，还检测了上皮-间质转化（EMT）标志物的表达以及Wnt7a启动子的高甲基化情况。Wnt7a在GC中表达下调，其表达与GC患者的不良预后相关。此外，上调Wnt7a显著抑制了GC细胞在体外和体内的生长、侵袭和转移能力。机制上，发现Wnt7a可抑制GC细胞的EMT过程。此外，Wnt7a表达降低是由于启动子内5'-CpG岛的甲基化所致。此外，Wnt7a在GC细胞中的肿瘤抑制作用独立于经典的Wnt/β-连环蛋白信号通路。总之，我们的研究结果表明，Wnt7a可用作GC诊断的潜在标志物和治疗靶点。
