MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38.
Liang X1, Liu Y2, Mei S2, Zhang M2, Xin J2, Zhang Y2, Yang R3.
1Department of Immunology, Nankai University School of Medicine, Tianjin, China; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.2Department of Immunology, Nankai University School of Medicine, Tianjin, China.3Department of Immunology, Nankai University School of Medicine, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China.
Dendritic cells (DCs) play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22) as a microRNA inhibiting p38 protein expression by directly binding to the 3′ untranslated region (3’UTR) of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.