1. Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs
- Author
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Ling Mao, Yan-qin Cai, Wei-xian Chen, Shanliang Zhong, Jianhua Zhao, Jianwei Zhou, Jinhai Tang, Jian Li, and Dan-dan Yu
- Subjects
0301 basic medicine ,Apoptosis ,Breast Neoplasms ,Drug resistance ,Docetaxel ,Bioinformatics ,Exosomes ,Green fluorescent protein ,03 medical and health sciences ,microRNA ,medicine ,Tumor Microenvironment ,Humans ,Gene ,Wnt Signaling Pathway ,business.industry ,Wnt signaling pathway ,Cancer ,Biological activity ,General Medicine ,medicine.disease ,Microvesicles ,Coculture Techniques ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Doxorubicin ,Drug Resistance, Neoplasm ,Cancer research ,MCF-7 Cells ,Female ,Taxoids ,business - Abstract
While adriamycin (adr) offers improvement in survival for breast cancer (BCa) patients, unfortunately, drug resistance is almost inevitable. Mounting evidence suggests that exosomes act as a vehicle for genetic cargo and constantly shuttle biologically active molecules including microRNAs (miRNAs) between heterogeneous populations of tumor cells, engendering a resistance-promoting niche for cancer progression. Our recent study showed that exosomes from docetaxel-resistance BCa cells could modulate chemosensitivity by delivering miRNAs. Herein, we expand on our previous finding and explore the relevance of exosome-mediated miRNA delivery in resistance transmission of adr-resistant BCa sublines. We now demonstrated the selective packing of miRNAs within the exosomes (A/exo) derived from adr-resistant BCa cells. The highly expressed miRNAs in A/exo were significantly increased in recipient fluorescent sensitive cells (GFP-S) after A/exo incorporation. Gene ontology analysis of predicted targets showed that the top 30 most abundant miRNAs in A/exo were involved in crucial biological processes. Moreover, A/exo not only loaded miRNAs for its production and release but also carried miRNAs associated with Wnt signaling pathway. Furthermore, A/exo co-culture assays indicated that miRNA-containing A/exo was able to increase the overall resistance of GFP-S to adr exposure and regulate gene levels in GFP-S. Our results reinforce our earlier reports that adr-resistant BCa cells could manipulate a more deleterious microenvironment and transmit resistance capacity through altering gene expressions in sensitive cells by transferring specific miRNAs contained within exosomes.
- Published
- 2015