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

Xue Liang1, Wenfeng Shangguan1, Miaomiao Zhang2

  • 1Department 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.

Insights

MicroRNA (miR)-128 enhances anti-tumor immunity by dendritic cells (DCs) through the p38 signaling pathway. This study shows miR-128 targets p38, modulating cytokine secretion and inhibiting melanoma tumor growth.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • MicroRNA (miR)-128 is a known tumor growth inhibitor.
  • Dendritic cells (DCs) play a crucial role in anti-tumor immunity.
  • The specific role of miR-128 in DC-mediated anti-tumor immunity requires further investigation.

Purpose of the Study:

  • To elucidate the association between miR-128 and DC-mediated anti-tumor immunity.
  • To investigate the mechanism by which miR-128 influences DC function.
  • To evaluate the therapeutic potential of modulating miR-128 in a melanoma model.

Main Methods:

  • Murine B16 melanoma cells and C57BL/6 mice were used.
  • Dendritic cells (DCs) were derived and stimulated with B16 cells.
  • miR-128 mimic/inhibitor and p38 inhibitor were transfected into DCs.
  • mRNA and protein expression of p38, and cytokine levels (IL-6, IL-10, IL-12) were analyzed.
  • Tumor growth and survival were assessed in a B16 melanoma mouse model.

Main Results:

  • B16 melanoma stimulation reduced miR-128 abundance and increased p38 protein expression in DCs.
  • miR-128 inhibited p38 protein expression in a dose-dependent manner, without affecting mRNA levels.
  • Modulation of miR-128 or p38 affected the secretion of IL-6, IL-10, and IL-12.
  • DCs engineered with miR-128 mimic or p38 inhibitor significantly reduced tumor growth and prolonged survival in mice.

Conclusions:

  • miR-128 regulates DC immune response via p38-downstream cytokines.
  • miR-128 enhances anti-tumor immunity of DCs by targeting the p38 mitogen-activated protein kinase signaling pathway.
  • Modulating miR-128 in DCs represents a potential strategy for melanoma immunotherapy.