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

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• 作者：Ying Ma^a ; ¹ ; Jiuyu Gong^a ; ^b ; ¹ ; Yuan Liu^a ; ^c ; Wenwei Guo^a ; ^c ; Boquan Jin^a ; Xiaohong Wang^c ; ^{xhwang_1968@126.com" class="auth_mail" title="E-mail the corresponding author} ; Lihua Chen^a ; ^{chenlh@fmmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Natural killer cell ; MicroRNA-30c ; NK group 2 ; member D (NKG2D) ; CD107a ; Fas ligand ; Cytotoxicity
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：151
• 期：Complete
• 页码：174-181
• 全文大小：1098 K

文摘

Natural killer (NK) cells play critical roles in antitumor immunity. Our previous study showed that over-expression of miR-30c-1* enhanced NKL cell cytotoxicity through up-regulation of tumor necrosis factor-α 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.