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- Title
Exosomal miR-331-3p derived from chemoresistant osteosarcoma cells induces chemoresistance through autophagy.
- Authors
Meng, Chenyang; Yang, Yun; Feng, Wei; Ma, Penglei; Bai, Rui
- Abstract
Background: Osteosarcoma is a common malignant bone tumor, and chemotherapy can effectively improve the prognosis. MicroRNA-331 (MiR-331) is associated with poor cancer outcomes. However, the role of miR-331 in osteosarcoma remains to be explored. Methods: Drug-resistant osteosarcoma cells were cultured, and their exosomes were purified. The secretion and uptake of exosomes by drug-resistant osteosarcoma and osteosarcoma cells were confirmed using a fluorescence tracking assay and Transwell experiments. The effects of drug-resistant exosomes on cell proliferation were determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. siRNA-Drosha and neutral sphingomyelinase inhibitor GW4869 were used to determine the transfer of miRNAs. qRT-PCR and western blotting were used to detect the role of autophagy in the regulation of drug-resistant cell-derived exosomal miR-331-3p. Results: Exosomal miR-331-3p levels in drug-resistant cells were higher than in exosomes from osteosarcoma cells. The exosomes secreted by the drug-resistant osteosarcoma cells could be absorbed by osteosarcoma cells, leading to acquired drug resistance in previously non-resistance cells. Inhibition of miRNAs resulted in reduced transmission of drug resistance transmission by exosomes. Exosomes from drug-resistant osteosarcoma cells transfected with siRNA-Drosha or treated by GW4869 could not enhance the proliferation of MG63 and HOS cells. Finally, miR-331-3p in the exosomes secreted by drug-resistant osteosarcoma cells could induce autophagy of osteosarcoma cells, allowing them to acquire drug resistance. The inhibition of miR-331-3p decreased drug resistance of osteosarcoma cells. Conclusion: Exosomes secreted from chemoresistant osteosarcoma cells promote drug resistance through miR-331-3p and autophagy. Inhibition of miR-331-3p could be used to alleviate drug resistance in osteosarcoma.
- Subjects
EXOSOMES; OSTEOSARCOMA; CANCER chemotherapy; AUTOPHAGY; WESTERN immunoblotting; MICRORNA; BONE tumors; GENE expression; TREATMENT effectiveness; RESEARCH funding; CELL proliferation; DESCRIPTIVE statistics; POLYMERASE chain reaction; CELL lines; DRUG resistance in cancer cells
- Publication
Journal of Orthopaedic Surgery & Research, 2023, Vol 18, Issue 1, p1
- ISSN
1749-799X
- Publication type
Article
- DOI
10.1186/s13018-023-04338-8