Overexpression of eEF1A1 regulates G1-phase progression to promote HCC proliferation through the STAT1-cyclin D1 pathway
Overexpression of eEF1A1 regulates G1-phase progression to promote HCC proliferation through the STAT1-cyclin D1 pathway
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eEF1A1 的过表达通过 STAT1-cyclin D1 途径调节 G1 期进展，促进 HCC 增殖
DOI：
10.1016/j.bbrc.2017.10.116
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发表时间：
2017-12-16
影响因子：
3.1
通讯作者：
Shao, Jianghua
中科院分区：
文献类型：
--
作者：
Huang, Jian;Zheng, Chuqian;Shao, Jianghua
肝细胞癌（HCC）是一种常见的恶性肿瘤，具有侵袭性和高度增殖性。研究证实肝癌细胞增殖与细胞周期的G1期有关，但详细的分子机制至今尚未完全阐明。真核翻译延伸因子1A1（eEF1A1）是一种进化上保守的延伸因子蛋白，参与肿瘤细胞增殖。然而，eEF1A1在肝癌中是通过调节细胞周期的哪个时相来影响细胞增殖的，其详细的分子机制尚不清楚。在本研究中，我们观察到eEF1A1通过调节细胞周期的G1期来影响HCC细胞的增殖。此外，eEF1A1通过调节cyclin D1的表达影响G1期，促进肝癌细胞在体外和体内的增殖。此外，我们的研究结果表明，eEF1A1调控细胞周期蛋白D1的表达通过STAT1信号。STAT1通过与细胞周期蛋白D1启动子结合来增加细胞周期蛋白D1的转录活性。综上所述，这些发现使我们能够确定一种新的机制，eEF1A1通过STAT1信号调节HCC中细胞周期的G1期，通过调节细胞周期蛋白D1的表达来促进肿瘤增殖。(C)2017爱思唯尔公司All rights reserved.
Hepatocellular carcinoma (HCC) is a common cancer worldwide with an aggressive and highly proliferative activity. Studies had confirmed that HCC cell proliferation is associated with the cell cycle's G1 phase, but the detailed molecular mechanism has not been thoroughly elucidated to date. Eukaryotic translation elongation factor 1A1 (eEF1A1) is an evolutionarily conserved elongation factor protein and is involved in tumor cell proliferation. However, which phase of the cell cycle is regulated by eEF1A1 to influence cell proliferation in HCC and its detailed molecular mechanism remain unclear. In this study, we observed that eEF1A1 influences HCC cell proliferation by regulating the cell cycle's G1 phase. In addition, eEF1A1 influences G1 phase by regulating cyclin D1 expression, promoting HCC cell proliferation both in vitro and in vivo. Moreover, our results indicated that eEF1A1 regulates cyclin D1 expression through STAT1 signaling. STAT1 increases the transcriptional activity of cyclin D1 by binding to the cyclin D1 promoter. Taken together, these findings enabled us to identify a novel mechanism by which eEF1A1 regulates the cell cycle's G1 phase to promote tumor proliferation by regulating cyclin D1 expression through STAT1 signaling in HCC. (C) 2017 Elsevier Inc. All rights reserved.