Guo Lei, Zhang Shumin, Zhang Bo, Chen Wanyong, Li Xiaoqiang, Zhang Wentao, Zhou Chenhao, Zhang Jubo, Ren Ning, Ye Qinghai
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Key Laboratory of Carcinogenesis and Cancer Invasion, Fundan University, Ministry of Education, Shanghai, 200032, China.
Cell Biol Toxicol. 2016 Aug;32(4):263-74. doi: 10.1007/s10565-016-9327-z. Epub 2016 May 30.
G2 and S phase-expressed-1 (GTSE1) was recently reported to upregulate in several types of human cancer, based on negatively regulate p53 expression. However, its expression and functional roles in hepatocellular carcinoma (HCC) remain unknown. In this study, GTSE1 was observed to be highly expressed in HCC specimens and cell lines both at messenger RNA (mRNA) and protein levels. Furthermore, high GTSE1 expression was positively associated with tumor size, venous invasion, advanced tumor stage, and short overall survival. Moreover, we generated stable GTSE1 knockdown HCC cell lines to explore the effects of GTSE1 silencing on the growth and invasion of HCC in vitro. In determining the pathway through which GTSE1 regulated cell proliferation and invasion, GTSE1 silencing was found to inhibit AKT phosphorylation and downregulated cell cycle-related protein. In addition, GTSE1 downregulation decreased the growth of xenografts. In conclusion, these results indicated for the first time that overexpression of GTSE1 was involved in the progress of HCC, enhancing proliferation and promoting cell invasion in HCC cells.
G2和S期表达蛋白1（GTSE1）最近有报道称，基于其对p53表达的负调控作用，在几种人类癌症中表达上调。然而，其在肝细胞癌（HCC）中的表达及功能作用尚不清楚。在本研究中，观察到GTSE1在HCC标本和细胞系中的信使核糖核酸（mRNA）和蛋白质水平均高表达。此外，GTSE1高表达与肿瘤大小、静脉侵犯、肿瘤晚期及总生存期短呈正相关。而且，我们构建了稳定敲低GTSE1的HCC细胞系，以探究GTSE1沉默对体外HCC生长和侵袭的影响。在确定GTSE1调控细胞增殖和侵袭的途径时，发现GTSE1沉默可抑制AKT磷酸化并下调细胞周期相关蛋白。此外，GTSE1下调降低了异种移植瘤的生长。总之，这些结果首次表明GTSE1的过表达参与了HCC的进展，增强了HCC细胞的增殖并促进了细胞侵袭。
