Advances in Clinical and Experimental Medicine
2019, vol. 28, nr 12, December, p. 1639–1645
Publication type: original article
Inhibition of eukaryotic initiation factor 3B suppresses proliferation and promotes apoptosis of chronic myeloid leukemia cells
1 Department of Hematology, Yijishan Hospital, First Affiliated Hospital of Wannan Medical College, Wuhu, China
2 Department of Oncology, Yijishan Hospital, First Affiliated Hospital of Wannan Medical College, Wuhu, China
Background. Eukaryotic translation initiation factor 3B (eIF3b) has been reported to be overexpressed in colon, bladder and prostate cancers as well as in glioblastoma. However, there is no report on any correlation of eIF3b gene expression with cell proliferation and apoptosis in chronic myeloid leukemia (CML).
Objectives. In this study, we evaluated the role of eIF3b in cell proliferation and apoptosis in CML.
Material and Methods. Samples from patients with CML and CML cell lines were used. Quantitative RT-PCR, siRNA transfection, flow cytometry, and western blot analysis were performed.
Results. Quantitative RT-PCR revealed that the expression of eIF3b mRNA in CML patients was higher than that in the non-malignant controls. The proliferation of CML cells decreased after transfection of the cells with siRNA. The proportion of cells in the G1 and S phases in the experimental group decreased after transfection, while the number of cells in the G2/M phase increased, as compared with the control group. The total cell apoptosis percentage in the sheIF3b group (transduction with lentivirus-anti-eIF3b in K562 cells) was higher than the shCtrl group (transduction with empty-vector lentivirus in K562 cells) after transfection. Caspase 3/7 activity was higher and the expression of anti-apoptotic protein BCL-2 was lower in the sheIF3b group than in the shCtrl group after transfection.
Conclusion. Our results suggest that downregulation of eIF3b expression inhibits proliferation and induces apoptosis in CML cells.
cell proliferation, eukaryotic initiation factor 3b, chronic myeloid leukemia
- Gutierrez LG, Noriega MF, Laudicina A, Quatrin M, Bengio RM, Larripa I. An unusual translocation, t(1;11)(q21;q23), in a case of chronic myeloid leukemia with a cryptic Philadelphia chromosome. Oncol Lett. 2017;13(5):3159–3162.
- Hinnebusch AG, Lorsch JR. The mechanism of eukaryotic translation initiation: New insights and challenges. Cold Spring Harb Perspect Biol. 2012;4(10). doi:10.1101/cshperspect.a011544
- Pestova TV, Kolupaeva VG. The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection. Genes Dev. 2002;16(22):2906–2922.
- Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: Mechanisms and biological targets. Cell. 2009;136(4):731–745.
- Silvera D, Formenti SC, Schneider RJ. Translational control in cancer. Nat Rev Cancer. 2010;10(4):254–266.
- Hagner PR, Schneider A, Gartenhaus RB. Targeting the translational machinery as a novel treatment strategy for hematologic malignancies. Blood. 2010;115(11):2127–2135.
- Spilka R, Ernst C, Mehta AK, Haybaeck J. Eukaryotic translation initiation factors in cancer development and progression. Cancer Lett. 2013;340(1):9–21.
- Mayeur GL, Fraser CS, Peiretti F, Block KL, Hershey JW. Characterization of eIF3k: A newly discovered subunit of mammalian translation initiation factor elF3. Eur J Biochem. 2003;270(20):4133–4139.
- Hinnebusch AG. eIF3: A versatile scaffold for translation initiation complexes. Trends Biochem Sci. 2006;31(10):553–562.
- Wang Z, Chen J, Sun J, Cui Z, Wu H. RNA interference-mediated silencing of eukaryotic translation initiation factor 3, subunit B (eIF3b) gene expression inhibits proliferation of colon cancer cells. World J Surg Oncol. 2012;10:119.
- Wang H, Ru Y, Sanchez-Carbayo M, Wang X, Kieft JS, Theodorescu D. Translation initiation factor eIF3b expression in human cancer and its role in tumor growth and lung colonization. Clin Cancer Res. 2013;19(11):2850–2860.
- Liang H, Ding X, Zhou C, et al. Knockdown of eukaryotic translation initiation factors 3B (eIF3b) inhibits proliferation and promotes apoptosis in glioblastoma cells. Neurol Sci. 2012;33(5):1057–1062.
- Apperley JF. Chronic myeloid leukaemia. Lancet. 2015;385(9976):1447–1459.
- Kavalerchik E, Goff D, Jamieson CH. Chronic myeloid leukemia stem cells. J Clin Oncol. 2008;26(17):2911–2915.
- Savona M, Talpaz M. Getting to the stem of chronic myeloid leukaemia. Nat Rev Cancer. 2008;8(5):341–350.
- Pestova TV, Kolupaeva VG, Lomakin IB, et al. Molecular mechanisms of translation initiation in eukaryotes. Proc Natl Acad Sci U S A. 2001;98(13):7029–7036.
- Lee AS, Kranzusch PJ, Cate JH. eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature. 2015;522(7554):111–114.
- Xu F, Xu CZ, Gu J, et al. Eukaryotic translation initiation factor 3B accelerates the progression of esophageal squamous cell carcinoma by activating beta-catenin signaling pathway. Oncotarget. 2016;7(28):43401–43411.
- Choi YJ, Lee YS, Lee HW, Shim DM, Seo SW. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res. 2017;6(3):186–193.