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

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.