MicroRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells

Abstract

Osteosarcoma (OS) is the most common cancer of the bone. Chemotherapy is commonly used for the clinical treatment of OS. However, chemoresistance to cisplatin [also known as diamminedichloridoplatinum (II) (DDP)] is a major obstacle for OS therapy, the underlying mechanism of which is not fully understood. The present study aimed to investigate the role of microRNA (miR)-199a-5p in the regulation of chemoresistance to DDP in OS cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the expression level of miR-199a-5p was significantly reduced in human OS MG63 cells. In addition, DDP treatment also upregulated the protein levels of light chain 3 (LC3)-II and Beclin1 as well as the ratio of LC3-II vs. LC3-I in MG63 cells, indicating that autophagy was activated. Restoration of miR-199a-5p expression promoted DDP-induced inhibition of MG63 cell proliferation and inhibited DDP-induced autophagy, as indicated by the reduced protein levels of LC3-II and Beclin1 and the ratio of LC3-II vs. LC3-I. Finally, luciferase reporter assay data revealed that miR-199a-5p directly targeted Beclin1 and negatively mediated Beclin1 expression at a post-transcriptional level in MG63 cells. In conclusion, our study suggests that miR-199a-5p promotes the cytotoxicity of DDP in OS cells via inhibition of autophagy. Therefore, miR-199a-5p/autophagy signaling is involved in chemoresistance and may become a potential target for the treatment of DDP.resistant OS.