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Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells

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Abstract

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.

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Abbreviations

eIF:

Eukaryotic translation initiation factor

eIF3D:

Eukaryotic translation initiation factor 3 subunit D

qRT-PCR:

Quantitative real-time PCR

AML:

Acute myeloid leukemia

DMEM:

Dulbecco’s Modified Eagle Medium

shRNA:

Short hairpin RNA

CMV:

Cytomegalovirus

GFP:

Green fluorescent protein

MOI:

Multiplicity of infection

TBST:

Tris-buffered saline with 0.1% Tween-20

SAPK:

Stress-activated protein kinase

JNK:

c-Jun N-terminal kinase

7-AAD:

7-aminoactinomycin D

ECL:

Enhanced chemiluminescence

MTT:

Methylthiazol tetrazolium

Lv-sheIF3D:

sheIF3D lentivirus

Lv-shCon:

Empty vector lentivirus

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Acknowledgements

The research was supported by the National Natural Science Foundation of China (No. 81573772, 81403263). This study was supported by the Science and Technology Development Projects (No: 2014GSF118141) and the Taishan Scholar Program of Shandong province.

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Authors and Affiliations

  1. Department of Hematology, Liaocheng People’s Hospital, Liaocheng, Shandong, 252000, People’s Republic of China

    Guo-zhen Liu, Ji-zhu Liu, Li Zhang, Shuang-jing Li, Tai-wu Xiao, Jing-xia Wang & Guang-yao Li

  2. School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, People’s Republic of China

    Xiao-qing Li

  3. Department of Hematology, School of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China

    Guang-yao Li

  4. Department of Pediatrics, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, The Ohio State University College of Medicine, 575 Children’s Cross Road, Columbus, OH, 43215, USA

    Yusen Liu

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  1. Guo-zhen Liu
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  2. Ji-zhu Liu
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Correspondence to Guang-yao Li or Yusen Liu.

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Liu, Gz., Liu, Jz., Li, Xq. et al. Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells. Mol Cell Biochem 438, 191–198 (2018). https://doi.org/10.1007/s11010-017-3127-5

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  • DOI: https://doi.org/10.1007/s11010-017-3127-5

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