Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
J Cell Mol Med. 2021 Mar;25(6):2994-3005. doi: 10.1111/jcmm.16340. Epub 2021 Feb 1.
Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), as the key component of the transcription initiation factor complex EIF4F, is significantly upregulated in multiple solid tumours, including lung cancer. However, the function and mechanism of EIF4G1 in the regulation of non-small-cell lung cancer (NSCLC) remain unclear. Here, using the clinical samples and the comprehensive survival analysis platforms Kaplan-Meier plotter, we observed aberrant upregulation of EIF4G1 in NSCLC tissues; furthermore, high expression of EIF4G1 showed association with low differentiation of lung cancer cells and poor overall survival in NSCLC patients. Non-small-cell lung cancer cell line A549 and H1703 stably infected with EIF4G1 shRNA were used to determine the function of EIF4G1 in regulating cell proliferation and tumorigenesis in vitro and in vivo. The results demonstrated that EIF4G1 promoted the G1/S transition of the cell cycle and tumour cell proliferation in non-small cell lung cancer. Mechanistically, EIF4G1 was found to regulate the expression and phosphorylation of mTOR (Ser2448), which mediates the tumorigenesis-promoting function of EIF4G1. The inhibition of mTOR attenuated the EIF4G1-induced development and progression of tumours. These findings demonstrated that EIF4G1 is a new potential molecular target for the clinical treatment of non-small cell lung cancer.
真核翻译起始因子 4 γ 1（EIF4G1）作为转录起始因子复合物 EIF4F 的关键组成部分，在多种实体瘤中（包括肺癌）显著上调。然而，EIF4G1 在调节非小细胞肺癌（NSCLC）中的功能和机制尚不清楚。在这里，我们使用临床样本和综合生存分析平台 Kaplan-Meier plotter，观察到 EIF4G1 在 NSCLC 组织中的异常上调；此外，EIF4G1 的高表达与肺癌细胞分化程度低和 NSCLC 患者总生存率低有关。使用稳定感染 EIF4G1 shRNA 的非小细胞肺癌细胞系 A549 和 H1703 来确定 EIF4G1 在体外和体内调节细胞增殖和肿瘤发生中的功能。结果表明，EIF4G1 促进非小细胞肺癌细胞周期的 G1/S 过渡和肿瘤细胞增殖。在机制上，发现 EIF4G1 调节 mTOR（Ser2448）的表达和磷酸化，mTOR 介导 EIF4G1 的促进肿瘤发生功能。mTOR 的抑制减弱了 EIF4G1 诱导的肿瘤发生和进展。这些发现表明，EIF4G1 是临床治疗非小细胞肺癌的一个新的潜在分子靶点。
