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

Mol Cell Biochem. 2018 Jan;438(1-2):191-198. doi: 10.1007/s11010-017-3127-5. Epub 2017 Aug 12.

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.

Keywords: Acute myeloid leukemia; Apoptosis; Cell proliferation; Growth arrest; RNA interference; Translational control; eIF3D.

MeSH terms

  • Cell Proliferation*
  • Eukaryotic Initiation Factor-3 / genetics
  • Eukaryotic Initiation Factor-3 / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • U937 Cells

Substances

  • EIF3D protein, human
  • Eukaryotic Initiation Factor-3
  • Neoplasm Proteins