miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting of p38

Liang,Xue; Shangguan,Wenfeng; Zhang,Miaomiao; Mei,Shiyue; Wang,Liyang; Yang,Rongcun

doi:10.3892/mmr.2017.6717

miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting of p38

Authors:
- Xue Liang
- Wenfeng Shangguan
- Miaomiao Zhang
- Shiyue Mei
- Liyang Wang
- Rongcun Yang
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Affiliations: Department of Cardiology, Tianjin Key Laboratory of Ionic‑Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China, State Key Laboratory of Medicinal Chemical Biology, School of Medicine, Nankai University, Tianjin 300071, P.R. China, Faculty of Medicine, University of Southampton, Southampton, Hampshire SO17 1BJ, UK
Published online on: June 7, 2017 https://doi.org/10.3892/mmr.2017.6717
Pages: 1307-1313
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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