MicroRNA-30c promotes natural killer cell cytotoxicity via up-regulating the expression level of NKG2D

被引:27
作者
Ma, Ying [1 ]
Gong, Jiuyu [1 ,2 ]
Liu, Yuan [1 ,3 ]
Guo, Wenwei [1 ,3 ]
Jin, Boquan [1 ]
Wang, Xiaohong [3 ]
Chen, Lihua [1 ]
机构
[1] Fourth Mil Med Univ, Dept Immunol, 169 Changle West Rd, Xian 710032, Peoples R China
[2] Hosp Hubei Armed Police Corps, Wuhan 430000, Hubei, Peoples R China
[3] Fourth Mil Med Univ, Tangdu Hosp, Dept Gynecol & Obstet, Xian 710038, Peoples R China
基金
中国国家自然科学基金;
关键词
Natural killer cell; MicroRNA-30c; NK group 2; member D (NKG2D); CD107a; Fas ligand; Cytotoxicity; NK CELLS; DIFFERENTIATION; ACTIVATION; RESISTANCE; INHIBITION; SIGNATURE; EFFECTOR; RECEPTOR; PATTERNS; SURVIVAL;
D O I
10.1016/j.lfs.2016.03.012
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: Natural killer (NK) cells play critical roles in antitumor immunity. Our previous study showed that overexpression of miR-30c-1* enhanced NKL cell cytotoxicity through up-regulation of tumor necrosis factor-a via directly targeting transcription factor homeobox containing 1. MiR-30c, the complimentary microRNA of miR-30c-1*, has been found to exert regulatory effect on T cell function. However, the effect of miR-30c on NK cells is unknown. Therefore, this study aimed to investigate whether miR-30c could play a role to enhance NK cell activation and cytotoxicity. Main methods: Chemosynthesis exogenous miR-30c mimics and miR-30c inhibitor were transfected into NKL cells and isolated human peripheral blood NK cells, respectively. The expression levels of NK group 2, member D (NKG2D), CD107a and FasL on cell surface and cytotoxic ability of miRNAs transfected NKL cells against SMMC-7721 cells were evaluated. Key findings: MiR-30c could increase the expression of NKG2D and CD107a on NKL cells, and enhance cytotoxic ability of NKL cells to kill SMMC-7721 cells. Moreover, miR-30c could up-regulate the expression of FasL on both NKL cells and human peripheral blood NK cells. However, the peripheral blood NK cells from only four in ten healthy donors appeared high expression levels of NKG2D and CD107a after miR-30c transfection. Significance: MiR-30c could promote the cytotoxicity of NKL cells in vitro by up-regulating the expression levels of NKG2D, CD107a and FasL. However, the effect of miR-30c on ex vivo NK cells from different human individuals is diverse, indicating that miR-30c may play complicate and fine adjustment in immune system. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:174 / 181
页数:8
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