MicroRNA-124 suppresses growth and aggressiveness of osteosarcoma and inhibits TGF-β-mediated AKT/GSK-3β/SNAIL-1 signaling

作者：Yu, Bo; Jiang, Kaibiao; Zhang, Jidong^*

来源：Molecular Medicine Reports, 2018, 17(5): 6736-6744.

DOI：10.3892/mmr.2018.8637

• microRNA-124
• osteosarcoma
• integrin
• apoptosis resistance
• transforming growth factor-beta
• AKT serine threonine kinase/glycogen synthase kinase-3 beta/snail family transcriptional repressor 1

Osteosarcoma is one of the most common malignant tumors in adolescent populations and the prognosis remains incompletely understand. Previous reports have demonstrated that microRNA-124 (miR-124) has inhibitory effects on various human malignancies and is associated with tumor progression. However, the clinical significance and potential mechanisms of miR-124 in the progression of osteosarcoma is not clearly understood. In this study, the potential molecular mechanism of miR-124 in osteosarcoma tumorigenesis, growth and aggressiveness was investigated. The growth, proliferation, apoptosis, migration and invasion of osteosarcoma cells were investigated following miR-124 transfection were determined by colony formation assay, western blotting, immunofluorescence, migration/invasion assays and reverse transcription-quantitative polymerase chain reaction. In vivo anti-cancer effects of miR-124 were analyzed by a tumor growth assay, immunohistochemistry and survival rate observations. The results demonstrated that miR-124 transfection significantly decreased integrin expression in osteosarcoma cells, and further inhibited growth, proliferation, migration and invasion of osteosarcoma cells. Flow cytometry assays indicated that miR-124 transfection attenuated apoptosis resistance of osteosarcoma to tunicamycin, potentially via the downregulation of P53 and Bcl-2 apoptosis regulator expression. Mechanistic assays demonstrated that miR-124 transfection suppressed TGF-beta expression in osteosarcoma. An animal study revealed that tumor growth was reduced in tumor cells transfected with miR-124 compared with control cells, and the survival rate was prolonged in mice with miR-124 transfected xenografts compared with control tumors. In conclusion, these results indicate that miR-124 transection inhibits the growth and aggressive of osteosarcoma, potentially via suppression of TGF-beta-mediated AKT/GSK-3 beta/snail family transcriptional repressor 1 (SNAIL-1) signaling, suggesting miR-124 may be a potential anti-cancer agent/target for osteosarcoma therapy.

• 出版日期2018-5
• 单位上海交通大学