Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating -Mediated Glycose Metabolism.

Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 () was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of , , , , and , decreased expression, and weakened the adriamycin resistance in resistant cells. miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target and promoted adriamycin resistance in BC cells. [Figure: see text].