MicroRNA‑33a‑5p overexpression sensitizes triple‑negative breast cancer to doxorubicin by inhibiting eIF5A2 and epithelial‑mesenchymal transition

Guan,Xiaoqing; Gu,Shucheng; Yuan,Mu; Zheng,Xiangxin; Wu,Ji

doi:10.3892/ol.2019.10984

MicroRNA‑33a‑5p overexpression sensitizes triple‑negative breast cancer to doxorubicin by inhibiting eIF5A2 and epithelial‑mesenchymal transition

Authors:
- Xiaoqing Guan
- Shucheng Gu
- Mu Yuan
- Xiangxin Zheng
- Ji Wu
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Affiliations: Department of Breast Surgery, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, Jiangsu 223800, P.R. China
Published online on: October 14, 2019 https://doi.org/10.3892/ol.2019.10984
Pages: 5986-5994
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Drug resistance is a significant obstacle when treating triple‑negative breast cancer (TNBC). Several studies have demonstrated that microRNAs (miRNAs) have essential roles in regulating drug resistance in different types of cancer. miR‑33a‑5p has previously been reported to be a tumor suppressor in several types of cancer. However, its role in breast cancer remains unknown. The present study aimed to investigate the role of miR‑33a‑5p in the chemoresistance of TNBC and uncover its potential molecular mechanisms. Cell Counting Kit‑8 assay was used to examine cell proliferation, reverse transcription‑quantitative PCR analysis was used to examine miR‑33a levels, and western blotting and immunofluorescence assays were used to examine the expression of epithelial‑mesenchymal transition (EMT)‑associated proteins and of eukaryotic translation initiation factor 5A2 (eIF5A2). The results indicated that miR‑33a‑5p expression was lower in TNBC cells compared with non‑TNBC cells. miR‑33a‑5p overexpression significantly improved the doxorubicin (Dox) sensitivity of TNBC cells, but not that of non‑TNBC cells. It was then observed that Dox treatment inhibited miR‑33a‑5p expression and induced EMT in TNBC cells, by increasing the expression levels of vimentin, while decreasing the expression levels of E‑cadherin. Furthermore, it was revealed that forced expression of miR‑33a‑5p attenuated Dox‑induced EMT. eIF5A2 was identified as a potential target of miR‑33a‑5p, and miR‑33a‑5p overexpression inhibited the expression of eIF5A2. eIF5A2 inhibition, via its inhibitor GC7, sensitized TNBC cells to Dox and reversed Dox‑induced EMT. Overall, the present study demonstrated that miR‑33a‑5p enhanced the sensitivity of TNBC cells to Dox, by suppressing eIF5A2 expression and reversing Dox‑induced EMT, providing a potential therapeutic target for treating drug‑resistant TNBC.

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