Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2

Chen,Junqing; Tian,Wei; He,Haifei; Chen,Feng; Huang,Jian; Wang,Xiaojia; Chen,Zhanhong

doi:10.3892/or.2018.6735

Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2

Authors:
- Junqing Chen
- Wei Tian
- Haifei He
- Feng Chen
- Jian Huang
- Xiaojia Wang
- Zhanhong Chen
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Affiliations: Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Breast Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Department of Breast Surgical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
Published online on: September 26, 2018 https://doi.org/10.3892/or.2018.6735
Pages: 3821-3829

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Abstract

Acquisition of resistance to paclitaxel is a major obstacle to successful treatment of breast cancer patients, but the molecular mechanisms underlying the development of drug resistance remain largely unclear. The aim of the present study was to investigate the role and mechanism of action of miR‑200c‑3p in the resistance of breast cancer to paclitaxel. It was observed that miR‑200c‑3p expression, as determined by reverse transcription‑quantitative polymerase chain reaction analysis, was significantly downregulated in paclitaxel‑resistant MCF‑7/Tax cells compared with parental MCF‑7 cells. Overexpression of miR‑200c‑3p increased the chemosensitivity to paclitaxel and enhanced apoptosis in MCF‑7/Tax cells, whereas the downregulation of miR‑200c‑3p exerted the opposite effect. In addition, upregulation of miR‑200c‑3p in MCF‑7/Tax cells suppressed the expression of sex‑determining region Y‑box 2 (SOX2) at the mRNA and protein levels. Dual‑luciferase reporter assay demonstrated that SOX2 is a target of miR‑200c‑3p in MCF‑7/Tax cells. Moreover, knockdown of SOX2 expression increased chemosensitivity to paclitaxel and upregulated miR‑200c‑3p expression in MCF‑7/Tax cells. Taken together, the results of the present study indicated that miR‑200c‑3p plays a key role in the development of paclitaxel resistance in breast cancer, possibly partially through regulating SOX2 expression, suggesting that the miR‑200c‑3p‑SOX2 loop may serve as a potential target for the reversal of paclitaxel resistance in breast cancer.

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