Down-regulation of RBP-J mediated by microRNA-133a suppresses dendritic cells and functions as a potential tumor suppressor in osteosarcoma.

ABSTRACT

BACKGROUND AND OBJECTIVE: In recent years, immunotherapy for the treatment of tumors have been established. Dendritic cells (DCs) are extremely efficient and professional antigen presenting cells (APCs), which are an important target for immune therapeutic interventions in cancer. In present study, we investigated whether RBP-J signaling regulated by miR-133a was involved in the DCs mediated tumor suppressor in osteosarcoma. METHODS: DCs were isolated from 30 osteosarcoma patients and 30 healthy subjects. Mouse macrophage-like cell line RAW264.7 were cultured and osteosarcoma mouse model with injection of murine osteosarcoma cell line S180 were established. RESULTS: In osteosarcoma patients, miR-133a expression level of DCs was increased, and RBP-J expression in mRNA and protein levels were decreased. MiR-133a inhibitor promoted maturation and activation of DCs in osteosarcoma patients. In osteosarcoma mouse model, miR-133a mimic suppressed the maturation and activation of spleen DCs, while miR-133a inhibitor promoted them. Overexpression of miR-133a decreased therapeutic effect of DCs on osteosarcoma mice. In RAW264.7 cells, miR-133a was observed to target RBP-J and regulate its expression. MiR-133a mimic inhibited the maturation of DCs in cells exposed to LPS, the effect of which was reversed by overexpression of RBP-J. CONCLUSION: RBP-J mediated by miR-133a probably contributed to the regulation of DCs maturation and activation in osteosarcoma, which functioned as a therapeutic target for the immunotherapy in cancers.