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miR-186 regulation of Twist1 and ovarian cancer sensitivity to cisplatin

Oncogene volume 35, pages 323–332 (2016)Cite this article

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Abstract

Epithelial–mesenchymal transition (EMT) has an established role in promoting tumor progression and the acquisition of therapeutic resistance. Here, the EMT phenotype was detected in cisplatin-resistant ovarian cancer tissues and cell lines, and correlated with decreased miR-186 expression, increased Twist1 expression, chemoresistance and poor prognosis in epithelial ovarian cancer (EOC) patients. Introducing miR-186 into EOC cells led to a reduction in twist family bHLH transcription factor 1 (Twist1) expression along with morphological, functional and molecular changes consistent with mesenchymal-to-epithelial transition, G1 cell-cycle arrest and enhanced cell apoptosis, which consequently rendered the cells more sensitive to cisplatin in vitro and in vivo. Furthermore, luciferase reporter and rescue assay results showed that the EMT and drug resistance reversal in response to miR-186 was mediated by Twist1. Collectively, these findings implicate miR-186 as an attractive candidate for overcoming chemoresistance in ovarian cancer therapy.

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Acknowledgements

This work was supported by the Natural Science Foundation of China (81402165/81301194), the Natural Science Foundation of Jiangsu Province (BK20131241), the Clinical Special Projects of Science and Technology Department of Jiangsu Province (BL2012059), the Research Projects of Jiangsu Provincial Health Department (H201451), the Maternal and Child Health Research Projects of Jiangsu Province (F201437/F201350/F201215) and the Social Development of Zhenjiang (SH2012057/SH2013025).

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Author notes

  1. X Zhu and H Shen: These authors contributed equally to this work.

Authors and Affiliations

  1. The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

    X Zhu, X Yin, Y Liu, X Lin, Y Xu & W Xu

  2. Jiangsu University, Zhenjiang, Jiangsu, China

    X Zhu, H Shen, C Xie, L Hui & Y Cao

  3. The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

    H Shen & Y Fang

  4. The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China

    L Long, M Li & Y Li

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  1. X Zhu
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Correspondence to W Xu or Y Li.

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Zhu, X., Shen, H., Yin, X. et al. miR-186 regulation of Twist1 and ovarian cancer sensitivity to cisplatin. Oncogene 35, 323–332 (2016). https://doi.org/10.1038/onc.2015.84

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