Exosomes mediated transfer of lncRNA UCA1 results in increased tamoxifen resistance in breast cancer cells

C.-G. Xu, M.-F. Yang, Y.-Q. Ren, C.-H. Wu, L.-Q. Wang

1^st Department of Oncology, the People’s Hospital of Shouguang, Shouguang, Shandong, China. liquanwang1@outook.com

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• Pharmacology

OBJECTIVE: In this study, we firstly compared the loading of urothelial carcinoma-associated 1 (UCA1) in exosomes between tamoxifen sensitive and tamoxifen resistant breast cancer cells and further investigated the role of exosomal transfer of UCA1 in the development of tamoxifen resistance in estrogen receptor (ER) positive breast cancer cells.

MATERIALS AND METHODS: Exosomes were isolated from the culture medium of tamoxifen sensitive MCF-7 cells and tamoxifen resistant LCC2 cells. QRT-PCR was performed to analyze UCA1 expression in cells and exosomes. CCK-8 assay, immunofluorescence staining of cleaved caspase-3 and flow cytometric analysis of annexin V/PI staining were used to assess tamoxifen sensitivity.

RESULTS: UCA1 is significantly increased not only in LCC2 cells, but also in exosomes released from LCC2 cells. The increase in exosomes is more evident than in cells. MCF-7 cells pretreated with exos/LCC2 had a significantly increased cell viability, a decreased expression of cleaved caspase-3 and a lower ratio of apoptosis after tamoxifen treatment. The exos/LCC2 with impaired UCA1 loading had significantly suppressed capability to promote tamoxifen resistance in MCF-7 cells.

CONCLUSIONS: UCA1 is significantly loaded in exosomes from tamoxifen resistant LCC2 cells. Exosomes mediated transfer of UCA1 can significantly increase tamoxifen resistance in ER-positive MCF-7 cells.

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