Knockdown of GTPBP4 inhibits cell growth and survival in human hepatocellular carcinoma and its prognostic significance.
Knockdown of GTPBP4 inhibits cell growth and survival in human hepatocellular carcinoma and its prognostic significance.
复制标题
DOI：
10.18632/oncotarget.21500
复制
发表时间：
2017-11-07
期刊：
影响因子：
--
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Liu WB;Jia WD;Ma JL;Xu GL;Zhou HC;Peng Y;Wang W
GTP结合蛋白4（GTPBP 4）是参与60 S亚基合成和成熟的GTP酶家族的新成员，与细胞增殖和生长密切相关。到目前为止，少数现有的研究发现GTPBP 4在癌症中具有矛盾的双重作用。GTPBP 4在肝细胞癌（HCC）中的表达水平是否与患者的预后有关，其功能和潜在的分子机制尚不清楚。本研究首次对上述问题进行了探讨。我们的研究结果表明，GTPBP 4在HCC中过表达，GTPBP 4的敲低抑制HCC细胞的增殖，损害集落形成能力，诱导细胞周期停滞在G2/M期，并促进细胞凋亡。此外，体内裸鼠移植瘤模型显示GTPBP 4基因敲减可显著抑制肝癌的发生。基因芯片和进一步的途径富集分析表明，ERBB信号通路是变化最显著的一个。更重要的是，GTPBP 4高表达水平与HCC患者的不良预后显著相关。综上所述，所有这些结果表明，GTPBP 4作为癌基因，在肝癌的发展中起着关键作用，这将是一个潜在的治疗靶点或肝癌的生物标志物。
GTP-binding protein 4 (GTPBP4), as a novel member of GTPases involved in the synthesis of 60S subunit and maturation, is closely related to cell proliferation and growth. Till now, a small number of existing studies have found a contradictory dual role of GTPBP4 in cancer. Whether the expression level of GTPBP4 in hepatocellular carcinoma (HCC) is associated with the patients’ prognosis or its function and underlying molecular mechanisms still remains unclear. In the present study, the above issues were explored for the first time. Our results showed that GTPBP4 was overexpressed in HCC and knockdown of GTPBP4 delayed cell proliferation, impaired colony formation ability, induced cell cycle arrest in G2/M period and promoted apoptosis in HCC cell lines. Besides, in vivo xenograft nude mice model revealed that GTPBP4 knockdown could significantly suppress HCC tumorigenesis. Gene microarray and further pathway enrichment analyses indicated that ERBB signaling pathway was the most significantly changed one. More importantly, high GTPBP4 expression level significantly correlated to the poor prognosis of HCC patients. Taken together, all these findings suggest that GTPBP4 serves as an oncogene and plays a pivotal role in HCC development, which will be a potential therapeutic target or a biomarker for HCC.
登录
查看更多内容
影响因子：
81.5
作者：
Llovet, Josep M.;Zucman-Rossi, Jessica;Gores, Gregory
通讯作者：
Gores, Gregory
通过 miRNA 和 mRNA 表达谱的综合分析确定 HepG2 细胞系的 RNA 表达特征
影响因子：
3.5
作者：
Bai, Yunfei;Xue, Ying;Lu, Zuhong
通讯作者：
Lu, Zuhong
肝癌中热休克蛋白 gp96 通过调节 Mdm2 E3 连接酶活性降低 p53 稳定性
影响因子：
9.7
作者：
Wu, Bo;Chu, Xiaoyu;Meng, Songdong
通讯作者：
Meng, Songdong
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
3.8
作者：
Anaya, Jordan
通讯作者：
Anaya, Jordan