Transfer of exosomal microRNAs confers doxorubicin resistance in osteosarcoma cells

Osteosarcoma (OS) is the commonest primary malignant bone tumor in children and adolescents. However, chemotherapy resistance is a major challenge for the treatment of OS. Exosomes have been reported to serve an increasingly important role in different stages of tumor progression and chemotherapy resistance. The present study investigated whether exosomes derived from doxorubicin-resistant OS cells (MG63/DXR) could be taken up in doxorubicin-sensitive OS cells (MG63) and induce a doxorubicin-resistant phenotype. MDR-1, as the specific mRNA of chemoresistance, can be transferred by exosomes from MG63/DXR cells to MG63 cells. In addition, the present study identified 2,864 differentially expressed miRNAs (456 upregulated and 98 downregulated with fold-change >2.0, P<5×10(−2), and FDR<0.05) in all three sets of exosomes from MG63/DXR cells and MG63 cells. The related miRNAs and pathways of exosomes involved in the doxorubicin resistance were identified by bioinformatic analysis. A total of 10 randomly selected exosomal miRNAs were dysregulated in exosomes from MG63/DXR cells relative to MG63 cells by reverse transcription-quantitative PCR detection. As a result, miR-143-3p was found high expressed in exosomes from doxorubicin-resistant OS cells compared with doxorubicin-sensitive OS cells and upregulation of exosomal miR-143-3p abundance associated with the poor chemotherapeutic response to OS cells. Briefly, transfer of exosomal miR-143-3p confers doxorubicin resistance in osteosarcoma cells.