NDLI: Exosomal miR-331-3p derived from chemoresistant osteosarcoma cells induces chemoresistance through autophagy

Content Provider	Springer Nature : BioMed Central
Author	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.
Related Links	https://josr-online.biomedcentral.com/counter/pdf/10.1186/s13018-023-04338-8.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13018-023-04338-8
Journal	Journal of Orthopaedic Surgery and Research
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2023-11-22
Access Restriction	Open
Subject Keyword	Orthopedics Surgical Orthopedics Osteosarcoma Exosome microRNA-331 Autophagy Chemosensitivity Chemoresistance
Content Type	Text
Resource Type	Article
Subject	Surgery Orthopedics and Sports Medicine
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3/2023

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