Yin Guozhi, Liu Zhikui, Wang Yufeng, Sun Liankang, Wang Liang, Yao Bowen, Liu Runkun, Chen Tianxiang, Niu Yongshen, Liu Qingguang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University No. 277 Yanta West Road, Xi'an 710061, China.
Am J Transl Res. 2019 Jun 15;11(6):3426-3437. eCollection 2019.
Zinc finger protein ZNF503 is an important regulator during developmental process and tumor initiation. ZNF503 drives tumor development and process and was cancer-specific dysregulated in cancers. However, its expression and function in hepatocellular carcinoma (HCC) still need to be studied and elucidated. In this study, we demonstrated for the first time that ZNF503 mRNA and protein was up-regulated in HCC tissues and cell lines. Clinical data showed that high ZNF503 was significantly correlated with poor prognostic features, including advanced TNM stage and venous invasion. Moreover, ZNF503 was identified as a potential 5-year prognostic marker of HCC patients. Notably, ZNF503 promoted migration, invasion and EMT progress. ZNF503 was recruited to GATA3 promoter and inhibited its expression. GATA3 inhibited HCC cells migration, invasion and EMT process. Furthermore, we demonstrated that ZNF503 expression was regulated by miR-495. In HCC tissues. MiR-495 has an inverse correlation with ZNF503 expression. Conclusively, our data revealed that ZNF503 promoted migration, invasion and EMT process through regulating GATA3 expression, which was regulated by miR-495, suggesting the potential therapeutic value for HCC.
锌指蛋白ZNF503是发育过程和肿瘤发生过程中的重要调节因子。ZNF503驱动肿瘤的发展进程,且在癌症中存在癌症特异性失调。然而,其在肝细胞癌(HCC)中的表达和功能仍有待研究和阐明。在本研究中,我们首次证明ZNF503 mRNA和蛋白在HCC组织和细胞系中上调。临床数据显示,高表达的ZNF503与不良预后特征显著相关,包括晚期TNM分期和静脉侵犯。此外,ZNF503被确定为HCC患者潜在的5年预后标志物。值得注意的是,ZNF503促进迁移、侵袭和上皮-间质转化进程。ZNF503被招募至GATA3启动子并抑制其表达。GATA3抑制HCC细胞的迁移、侵袭和上皮-间质转化进程。此外,我们证明ZNF503的表达受miR-495调控。在HCC组织中,miR-495与ZNF503的表达呈负相关。总之,我们的数据表明ZNF503通过调节GATA3的表达促进迁移、侵袭和上皮-间质转化进程,而GATA3的表达受miR-495调控,这提示了其对HCC的潜在治疗价值。