Huang Jian, Zheng Chuqian, Shao Jun, Chen Leifeng, Liu Xiuxia, Shao Jianghua
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China; Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330006, China.
Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330006, China.
Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):542-549. doi: 10.1016/j.bbrc.2017.10.116. Epub 2017 Oct 24.
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.
肝细胞癌（HCC）是全球常见的癌症，具有侵袭性和高度增殖活性。研究证实，HCC细胞增殖与细胞周期的G1期相关，但迄今为止，详细的分子机制尚未完全阐明。真核生物翻译延伸因子1A1（eEF1A1）是一种进化保守的延伸因子蛋白，参与肿瘤细胞增殖。然而，eEF1A1在细胞周期的哪个阶段发挥作用以影响HCC细胞增殖及其详细分子机制仍不清楚。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细胞增殖。此外，eEF1A1通过调节细胞周期蛋白D1的表达影响G1期，在体外和体内均促进HCC细胞增殖。此外，我们的结果表明，eEF1A1通过STAT1信号通路调节细胞周期蛋白D1的表达。STAT1通过与细胞周期蛋白D1启动子结合增加其转录活性。综上所述，这些发现使我们能够确定一种新的机制，即eEF1A1通过STAT1信号通路调节细胞周期蛋白D1的表达，从而调节细胞周期的G1期以促进HCC肿瘤增殖。
