miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting of p38.
miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting of p38.
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miR-128 通过靶向 p38 增强树突状细胞介导的抗肿瘤免疫
DOI：
10.3892/mmr.2017.6717
复制
发表时间：
2017-08
影响因子：
3.4
通讯作者：
Yang R
中科院分区：
文献类型：
--
作者：
Liang X;Shangguan W;Zhang M;Mei S;Wang L;Yang R
miRNA（miR）-128是公认的肿瘤生长抑制因子，参与树突状细胞（DCs）的抗肿瘤作用。然而，miR-128与DC介导的抗肿瘤免疫之间的关联仍有待阐明。小鼠B16黑色素瘤细胞和C57 BL/6雄性小鼠用于获得骨髓源性DC。用B16细胞悬液处理DC。将miR-128模拟物、miR-128抑制剂、p38抑制剂或阴性对照寡核苷酸转染到DC中。逆转录-定量聚合酶链反应（RT-PCR）和免疫印迹法（Western blotting）检测转染后DCs中p38 mRNA和蛋白的表达。本研究表明，B16（黑色素瘤细胞系）刺激显著减弱了DC中miR-128的丰度，并增加了p38的蛋白表达水平。此外，miR-128以剂量依赖性方式抑制DC中p38的蛋白表达，但未观察到对p38 mRNA水平的显著影响。此外，miR-128模拟物或p38抑制剂降低了DC中白细胞介素（IL）-6和IL-10细胞因子的mRNA表达和分泌，并增加了DC中IL-12的水平，而miR-128抑制剂表现出相反的作用。这些结果表明，miR-128通过p38下游细胞因子调节DC的免疫应答。此外，在携带B16黑色素瘤的C57 BL/6小鼠中注射携带miR-128模拟物或p38抑制剂的DC后，肿瘤生长速率、大小和重量显著降低，存活时间延长。因此，结果表明，miR-128通过靶向p38丝裂原活化蛋白激酶信号通路增强DC的抗肿瘤免疫应答。
MiRNA (miR)-128, which is a well-recognized inhibitor of tumor growth, is involved in the anti-tumor function of dendritic cells (DCs). However, the association between miR-128 and the DC-mediated anti-tumor immunity remains to be elucidated. Murine B16 melanoma cells and C57BL/6 male mice were used to obtain marrow-derived DCs. DCs were treated with B16 cell suspension. miR-128 mimic, miR-128 inhibitor, p38 inhibitor or negative control oligonucleotides were transfected into DCs. After transfection, mRNA and protein expression of p38 in DCs was detected via reverse transcription-quantitative polymerase chain reaction and western blotting. The present study demonstrated that the miR-128 abundance in DCs was significantly attenuated by B16 (a melanoma cell line) stimulation and the protein expression level of p38 was increased. Additionally, miR-128 inhibited the protein expression of p38 in DCs in a dose-dependent manner, however no significant effect on the p38 mRNA level was observed. Furthermore, miR-128 mimic or p38 inhibitor decreased the mRNA expression and secretion of interleukin (IL)-6 and IL-10 cytokines and increased the level of IL-12 in DCs, whereas an miR-128 inhibitor exhibited the opposite effects. These findings suggested that miR-128 regulated the immune response of DCs via p38-downstream cytokines. Furthermore, the tumor growth rate, size and weight were markedly decreased and the survival time prolonged, following injection of DCs harboring miR-128 mimic or p38 inhibitor in C57BL/6 mice bearing B16 melanoma. The results therefore suggest that miR-128 enhances the anti-tumor immunity response of DCs via targeting of the p38 mitogen activated protein kinase signaling pathway.
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DOI：
10.1038/nrc3258
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.2
作者：
Oshita C;Takikawa M;Kume A;Miyata H;Ashizawa T;Iizuka A;Kiyohara Y;Yoshikawa S;Tanosaki R;Yamazaki N;Yamamoto A;Takesako K;Yamaguchi K;Akiyama Y
通讯作者：
Akiyama Y
影响因子：
4.4
作者：
Park, SJ;Nakagawa, T;Hirano, T
通讯作者：
Hirano, T
影响因子：
11.2
作者：
Godlewski, Jakub;Nowicki, Michal O.;Lawler, Sean
通讯作者：
Lawler, Sean
影响因子：
82.9
作者：
Nestle, FO;Alijagic, S;Schadendorf, D
通讯作者：
Schadendorf, D