Department of Hematology, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, People's Republic of China.
School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, People's Republic of China.
Mol Cell Biochem. 2018 Jan;438(1-2):191-198. doi: 10.1007/s11010-017-3127-5. Epub 2017 Aug 12.
Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia.
各种真核翻译起始因子（eIFs）已被牵涉到癌的发展中。真核翻译起始因子 3 亚基 D（eIF3D）最近被证明可以调节几种类型的人类癌细胞的生长。然而，eIF3D 在急性髓系白血病（AML）中的功能仍不清楚。在这项研究中，我们研究了 eIF3D 在三个 AML 细胞系和一个淋巴母细胞系中的表达，发现 eIF3D 在所有四个白血病细胞系中均有表达。为了探讨 eIF3D 在 AML 细胞增殖中的作用，我们应用慢病毒介导的 RNA 干扰技术敲低了 U937 细胞中 eIF3D 的表达。定量实时 PCR（qRT-PCR）和 Western blot 分析证实，eIF3D 敲低后 U937 细胞中 eIF3D 的表达显著下调。eIF3D 敲低显著抑制了 U937 细胞的增殖。此外，流式细胞术分析显示，eIF3D 沉默诱导细胞周期停滞在 G2/M 期，最终导致细胞凋亡。我们的结果表明，eIF3D 在 AML 细胞的增殖中起着关键作用，并提示 eIF3D 沉默可能是白血病的一种潜在治疗策略。
