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Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells

  • Authors:
    • Young‑Shin Lee
    • Woong Heo
    • Cheol‑Hun Son
    • Chi‑Dug Kang
    • You‑Soo Park
    • Jaeho Bae
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Gyeongsangnam 50612, Republic of Korea, Department of Research Center, Dongnam Institute of Radiological and Medical Sciences, Gijang, Busan 46033, Republic of Korea
    Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3301-3307
    |
    Published online on: August 9, 2019
       https://doi.org/10.3892/mmr.2019.10583
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Abstract

c‑Myc is a characteristic oncogene with dual functions in cell proliferation and apoptosis. Since the overexpression of the c‑Myc proto‑oncogene is a common event in the development and growth of various human types of cancer, the present study investigated whether oncogenic c‑Myc can alter natural killer (NK) cell‑mediated immunity through the expression of associated genes, using PCR, western blotting and flow cytometry assays. Furthermore, whether c‑Myc could influence the expression levels of natural killer group 2 member D (NKG2D) ligands, which are well known NK activation molecules, as well as NK cell‑mediated immunity, was investigated. c‑Myc was inhibited by 10058‑F4 treatment and small interfering RNA transfection. Upregulation of c‑Myc was achieved by transfection with a pCMV6‑myc vector. The inhibition of c‑Myc increased MHC class I polyeptide‑related sequence B and UL16 binding protein 1 expressions among NKG2D ligands, and the overexpression of c‑Myc suppressed the expression of all NKG2D ligands, except MHC class I polyeptide‑related sequence A. Furthermore, the alteration of c‑Myc activity altered the susceptibility of K562 cells to NK cells. These results suggested that the overexpression of c‑Myc may contribute to the immune escape of cancer cells and cell proliferation. Combined treatment with NK‑based cancer immunotherapy and inhibition of c‑Myc may achieve improved therapeutic results.
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1 

Shortt J and Johnstone RW: Oncogenes in cell survival and cell death. Cold Spring Harb Perspect Biol. 4(pii): a0098292012.PubMed/NCBI

2 

Dang CV: MYC on the path to cancer. Cell. 149:22–35. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Vennstrom B, Sheiness D, Zabielski J and Bishop JM: Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29. J Virol. 42:773–779. 1982.PubMed/NCBI

4 

Zech L, Haglund U, Nilsson K and Klein G: Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer. 17:47–56. 1976. View Article : Google Scholar : PubMed/NCBI

5 

Dang CV: c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol. 19:1–11. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Grandori C and Eisenman RN: Myc target genes. Trends Biochem Sci. 22:177–181. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL and Spies T: Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 285:727–729. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Diefenbach A, Jamieson AM, Liu SD, Shastri N and Raulet DH: Ligands for the murine NKG2D receptor: Expression by tumor cells and activation of NK cells and macrophages. Nat Immunol. 1:119–216. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Groh V, Bahram S, Bauer S, Herman A, Beauchamp M and Spies T: Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA. 93:12445–12450. 1996. View Article : Google Scholar : PubMed/NCBI

10 

Bakker AB, Phillips JH, Figdor CG and Lanier LL: Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific CTL. J Immunol. 160:5239–5245. 1998.PubMed/NCBI

11 

Chang CC and Ferrone S: NK cell activating ligands on human malignant cells: Molecular and functional defects and potential clinical relevance. Semin Cancer Biol. 16:383–392. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Hilpert J, Grosse-Hovest L, Grunebach F, Buechele C, Nuebling T, Raum T, Steinle A and Salih HR: Comprehensive analysis of NKG2D ligand expression and release in leukemia: Implications for NKG2D-mediated NK cell responses. J Immunol. 189:1360–1371. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Bae JH, Kim JY, Kim MJ, Chang SH, Park YS, Son CH, Park SJ, Chung JS, Lee EY, Kim SH and Kang CD: Quercetin enhances susceptibility to NK cell-mediated lysis of tumor cells through induction of NKG2D ligands and suppression of HSP70. J Immunother. 33:391–401. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Boissel N, Rea D, Tieng V, Dulphy N, Brun M, Cayuela JM, Rousselot P, Tamouza R, Le Bouteiller P, Mahon FX, et al: BCR/ABL oncogene directly controls MHC class I chain-related molecule A expression in chronic myelogenous leukemia. J Immunol. 176:5108–5116. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Heo W, Lee YS and Bae JH: Inhibition of oncogenes affects the expression of NKG2D ligands in cancer cells. J Life Sci. 23:1216–1222. 2013. View Article : Google Scholar

16 

Peinado C, Kang X, Hardamon C, Arora S, Mah S, Zhang H, Ngolab J and Bui JD: The nuclear factor-κB pathway down-regulates expression of the NKG2D ligand H60a in vitro: Implications for use of nuclear factor-κB inhibitors in cancer therapy. Immunology. 139:265–274. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Park SW, Bae JH, Kim SD, Son YO, Kim JY, Park HJ, Lee CH, Park DY, Kim JY, Lee MK, et al: Comparison of level of NKG2D ligands between normal and tumor tissue using multiplex RT-PCR. Cancer Invest. 25:299–307. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Huang MJ, Cheng YC, Liu CR, Lin S and Liu HE: A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp Hematol. 34:1480–1489. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Albajar M, Gómez-Casares MT, Llorca J, Mauleon I, Vaqué JP, Acosta JC, Bermudez A, Donato N, Delgado MD and León J: MYC in chronic myeloid leukemia: Induction of aberrant DNA synthesis and association with poor response to imatinib. Mol Cancer Res. 9:564–576. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Coulis CM, Lee C, Nardone V and Prokipcak RD: Inhibition of c-myc expression in cells by targeting an RNA-protein interaction using antisense oligonucleotides. Mol Pharmacol. 57:485–494. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Lozzio CB and Lozzio BB: Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 45:321–334. 1975.PubMed/NCBI

22 

Law JC, Ritke MK, Yalowich JC, Leder GH and Ferrell RE: Mutational inactivation of the p53 gene in the human erythroid leukemic K562 cell line. Leuk Res. 17:1045–1050. 1993. View Article : Google Scholar : PubMed/NCBI

23 

Zindy F, Eischen CM, Randle DH, Kamijo T, Cleveland JL, Sherr CJ and Roussel MF: Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev. 12:2424–2433. 1998. View Article : Google Scholar : PubMed/NCBI

24 

Campoli M and Ferrone S: Tumor escape mechanisms: Potential role of soluble HLA antigens and NK cells activating ligands. Tissue Antigens. 72:321–334. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Dunn GP, Bruce AT, Ikeda H, Old LJ and Schreiber RD: Cancer immunoediting: From immunosurveillance to tumor escape. Nat Immunol. 3:991–998. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Eisele G, Wischhusen J, Mittelbronn M, Meyermann R, Waldhauer I, Steinle A, Weller M and Friese MA: TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells. Brain. 129:2416–2425. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Groh V, Wu J, Yee C and Spies T: Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 419:734–738. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Xu L, Chen X, Shen M, Yang DR, Fang L, Weng G, Tsai Y, Keng PC, Chen Y and Lee SO: Inhibition of IL-6-JAK/Stat3 signaling in castration-resistant prostate cancer cells enhances the NK cell-mediated cytotoxicity via alteration of PD-L1/NKG2D ligand levels. Mol Oncol. 12:269–286. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Gasser S, Orsulic S, Brown EJ and Raulet DH: The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature. 436:1186–1190. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Nanbakhsh A, Pochon C, Mallavialle A, Amsellem S, Bourhis JH and Chouaib S: c-Myc regulates expression of NKG2D ligands ULBP1/2/3 in AML and modulates their susceptibility to NK-mediated lysis. Blood. 123:3585–3595. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lee YS, Heo W, Son CH, Kang CD, Park YS and Bae J: Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells. Mol Med Rep 20: 3301-3307, 2019.
APA
Lee, Y., Heo, W., Son, C., Kang, C., Park, Y., & Bae, J. (2019). Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells. Molecular Medicine Reports, 20, 3301-3307. https://doi.org/10.3892/mmr.2019.10583
MLA
Lee, Y., Heo, W., Son, C., Kang, C., Park, Y., Bae, J."Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells". Molecular Medicine Reports 20.4 (2019): 3301-3307.
Chicago
Lee, Y., Heo, W., Son, C., Kang, C., Park, Y., Bae, J."Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells". Molecular Medicine Reports 20, no. 4 (2019): 3301-3307. https://doi.org/10.3892/mmr.2019.10583
Copy and paste a formatted citation
x
Spandidos Publications style
Lee YS, Heo W, Son CH, Kang CD, Park YS and Bae J: Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells. Mol Med Rep 20: 3301-3307, 2019.
APA
Lee, Y., Heo, W., Son, C., Kang, C., Park, Y., & Bae, J. (2019). Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells. Molecular Medicine Reports, 20, 3301-3307. https://doi.org/10.3892/mmr.2019.10583
MLA
Lee, Y., Heo, W., Son, C., Kang, C., Park, Y., Bae, J."Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells". Molecular Medicine Reports 20.4 (2019): 3301-3307.
Chicago
Lee, Y., Heo, W., Son, C., Kang, C., Park, Y., Bae, J."Upregulation of Myc promotes the evasion of NK cell‑mediated immunity through suppression of NKG2D ligands in K562 cells". Molecular Medicine Reports 20, no. 4 (2019): 3301-3307. https://doi.org/10.3892/mmr.2019.10583
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