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

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.

The emerging role of miR‐128 in musculoskeletal diseases

“…In tumor development and some other inflammatory diseases such as asthma and infection, miR‐128 might play a positive role in the development of these diseases or pathological conditions. According to one report, miR‐128 enhanced antitumor immunity by targeting p38 in the dendritic cells, which originated from hematopoietic stem cells (Liang et al, 2017). Moreover, reduced miR‐128 resulted in more severe equine asthma through stimulating a Th2/Th17 type immune response (Pacholewska et al, 2017).…”

“…Overexpression of miR-128 aggravated TNF-α-induced inflammatory response in BMSCs and doxorubicininduced liver injury by regulating SIRT1 expression (L.. Another study demonstrated that overexpression of miR-128 increased the expression of genes associated with proinflammatory cytokines and fibrosis in rat kidney cells in vitro(Shyamasundar et al, 2018). In macrophages RAW264.7 (osteoclast progenitors), miR-128 was positively correlated with oxidized low-density lipoprotein (ox-LDL)-induced inflammation and oxidative stress (D. D.. Conversely, downregulation of miR-128 rescued the effects of ischemia hypoxia via regulating IL-33/sST2(Yang et al, 2019).In tumor development and some other inflammatory diseases such as asthma and infection, miR-128 might play a positive role in the development of these diseases or pathological conditions.According to one report, miR-128 enhanced antitumor immunity by targeting p38 in the dendritic cells, which originated from hematopoietic stem cells(Liang et al, 2017). Moreover, reduced miR-128 resulted in more severe equine asthma through stimulating a Th2/Th17 type immune response(Pacholewska et al, 2017).…”

gga-miR-155 Enhances Type I Interferon Expression and Suppresses Infectious Burse Disease Virus Replication via Targeting SOCS1 and TANK

“…Although it was reported that several miRNAs are involved in regulating IBDV replication by targeting viral genomic RNA or host cell proteins (Wang et al, 2013 ; Ouyang et al, 2015 ), the effect of miRNAs on IBDV replication and the underlying mechanisms are still unclear. In this study, we evaluated the miRNA expression profile in DF-1 cells in response to IBDV infection and selected 11 candidate miRNAs for further analysis, and the 11 candidate miRNAs play important roles in host immunity (Gu et al, 2015 ; Hosokawa et al, 2015 ; Lamontagne et al, 2015 ; Lind et al, 2015 ; Tan et al, 2015 ; Wu et al, 2015 ; Gonzalez-Martin et al, 2016 ; Peng et al, 2016 ; Yan et al, 2016 ; Liang et al, 2017 ; Liu et al, 2017 ). Through TCID 50 assay, we found that only gga-miR-155 significantly suppressed IBDV replication.…”

miRNA-128 modulates bone neoplasms cells proliferation and migration through the WNT/β-catenin and EMT signal pathways

“…Previous findings provided the evidence that miR-128 may serve as a potential therapeutic target in glioma by inhibition of tumor angiogenesis via p70S6K1 [ 35 ]. In addition, miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting p38 mitogen activated protein kinase (MAPK) signaling pathway in C57BL/6 mice bearing B16 melanoma [ 36 ]. Data in this study found that miR-128 knockdown inhibits bone cancer cells proliferation, migration, invasion, and promotes apoptosis and cell cycle.…”