Abstract:
BACKGROUND:Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. METHODS:Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. RESULTS:Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. CONCLUSIONS:Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Liu J,Zhu S,Tang W,Huang Q,Mei Y,Yang Hdoi
10.1186/s12935-020-01659-0subject
Has Abstractpub_date
2021-01-15 00:00:00pages
55issue
1issn
1475-2867pii
10.1186/s12935-020-01659-0journal_volume
21pub_type
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journal_title:Cancer cell international
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doi:10.1186/1475-2867-8-3
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journal_title:Cancer cell international
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journal_title:Cancer cell international
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doi:10.1186/s12935-019-0955-2
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pub_type: 杂志文章
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pub_type: 撤回出版物
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pub_type: 杂志文章
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pub_type: 杂志文章
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