Epstein-Barr virus-encoded microRNA BART7 downregulates major histocompatibility complex class I chain-related peptide A and reduces the cytotoxicity of natural killer cells to nasopharyngeal carcinoma

被引:26
作者
Wong, Thian-Sze [1 ]
Chen, Siqi [1 ]
Zhang, Min-Juan [1 ]
Chan, Jimmy Yu-Wai [1 ]
Gao, Wei [1 ]
机构
[1] Univ Hong Kong, Dept Surg, 102 Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China
关键词
nasopharyngeal carcinoma; Epstein-Barr virus; microRNA; BART7; natural killer cells; CD8(+) T-CELLS; IMMUNE EVASION; NK CELLS; NKG2D; ACTIVATION; RECEPTOR; PATHWAY; GROWTH; MICA;
D O I
10.3892/ol.2018.9041
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Evasion from natural killer (NK) cell surveillance enables cancer to proliferate and spread at the early stages. NK cells mediate specific cytolysis by activation of the triggering receptors on their cell surface, of which the communication between natural killer group 2, member D (NKG2D) and major histocompatibility complex class I chain-related peptide A (MICA) is a key regulatory axis. It has been indicated that cancer cells can reduce the surface expression of MICA, which thereby reduces the cytotoxicity of NK cells. In nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains unclear. The present study indicated that MICA expression in NPC was regulated by TGF1. Furthermore, the human MICA gene was demonstrated to contain the c-Myc binding site in the promoter region. Notably, the results suggested that TGF1 upregulated MICA expression by promoting c-Myc expression. Additionally, the findings demosntrated that TGF1 expression in NPC was negatively controlled by Epstein-Barr virus-encoded microRNA BART7 (ebv-miR-BART7). In ebv-miR-BART7-expressing NPC, the TGF1/c-Myc/MICA regulatory axis was significantly inhibited. Notably, functional analysis indicated that NPC cells expressing ebv-miR-BART7 were less sensitive to the cytolysis mediated by NK cells. In conclusion, the present results revealed that ebv-miR-BART7-expressing NPC may impair NK cells recognition and activity, which suggests that targeting ebv-miR-BART7 may be a useful therapeutic strategy in NPC immunotherapy.
引用
收藏
页码:2887 / 2892
页数:6
相关论文
共 29 条
  • [1] Epstein-Barr virus microRNAs reduce immune surveillance by virus-specific CD8+ T cells
    Albanese, Manuel
    Tagawa, Takanobu
    Bouvet, Mickael
    Maliqi, Liridona
    Lutter, Dominik
    Hoser, Jonathan
    Hastreiter, Maximilian
    Hayes, Mitch
    Sugden, Bill
    Martin, Larissa
    Moosmann, Andreas
    Hammerschmidt, Wolfgang
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (42) : E6467 - E6475
  • [2] Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA
    Bauer, Stefan
    Groh, Veronika
    Wu, Jun
    Steinle, Alexander
    Phillips, Joseph H.
    Lanier, Lewis L.
    Spies, Thomas
    [J]. JOURNAL OF IMMUNOLOGY, 2018, 200 (07) : 2231 - 2233
  • [3] TGF-β downregulates the activating receptor NKG2D on NK cells and CD8+ T cells glioma patients
    Crane, Courtney A.
    Han, Seunggu J.
    Barry, Jeffery J.
    Ahn, Brian J.
    Lanier, Lewis L.
    Parsa, Andrew T.
    [J]. NEURO-ONCOLOGY, 2010, 12 (01) : 7 - 13
  • [4] Epstein-Barr virus encoded microRNA BART7 regulates radiation sensitivity of nasopharyngeal carcinoma
    Gao, Wei
    Li, Zeng-Hong
    Chen, Siqi
    Chan, Jimmy Yu-Wai
    Yin, Min
    Zhang, Min-Juan
    Wong, Thian-Sze
    [J]. ONCOTARGET, 2017, 8 (12) : 20297 - 20308
  • [5] Costimulation of CD8αβ T cells by NKG2D via engagement by MIC induced on virus-infected cells
    Groh, V
    Rhinehart, R
    Randolph-Habecker, J
    Topp, MS
    Riddell, SR
    Spies, T
    [J]. NATURE IMMUNOLOGY, 2001, 2 (03) : 255 - 260
  • [6] Targeting natural killer cells in cancer immunotherapy
    Guillerey, Camille
    Huntington, Nicholas D.
    Smyth, Mark J.
    [J]. NATURE IMMUNOLOGY, 2016, 17 (09) : 1025 - 1036
  • [7] A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates
    Hislop, Andrew D.
    Ressing, Maaike E.
    van Leeuwen, Daphne
    Pudney, Victoria A.
    Horst, Danielle
    Koppers-Lalic, Danijela
    Croft, Nathan P.
    Neefjes, Jacques J.
    Rickinson, Alan B.
    Wiertz, Emmanuel J. H. J.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) : 1863 - 1873
  • [8] Impairment of natural killer cell and dendritic cell functions by the soluble form of MHC class I-related chain A in advanced human hepatocellular carcinomas
    Jinushi, M
    Takehara, T
    Tatsumi, T
    Hiramatsu, N
    Sakamori, R
    Yamaguchi, S
    Hayashi, N
    [J]. JOURNAL OF HEPATOLOGY, 2005, 43 (06) : 1013 - 1020
  • [9] Regulation of the expression of the liver cancer susceptibility gene MICA by microRNAs
    Kishikawa, Takahiro
    Otsuka, Motoyuki
    Yoshikawa, Takeshi
    Ohno, Motoko
    Takata, Akemi
    Shibata, Chikako
    Kondo, Yuji
    Akanuma, Masao
    Yoshida, Haruhiko
    Koike, Kazuhiko
    [J]. SCIENTIFIC REPORTS, 2013, 3
  • [10] Elevated TGF-β1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients
    Lee, JC
    Lee, KM
    Kim, DW
    Heo, DS
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 172 (12) : 7335 - 7340