Oncotarget

Research Papers:

Shikonin reduces tamoxifen resistance through long non-coding RNA uc.57

Chen-Han Zhang, Jue Wang, Lin-Xin Zhang, Yi-Han Lu, Tian-Hao Ji, Lu Xu and Li-Jun Ling _

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Oncotarget. 2017; 8:88658-88669. https://doi.org/10.18632/oncotarget.20809

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Abstract

Chen-Han Zhang1,*, Jue Wang1,*, Lin-Xin Zhang1,*, Yi-Han Lu1, Tian-Hao Ji1, Lu Xu and Li-Jun Ling1

1Breast disease division, First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, China

*These authors contributed equally to this work

Correspondence to:

Li-Jun Ling, email: linglijun@njmu.edu.cn

Keywords: shikonin, tamoxifen resistance, lncRNA, BCL11A, breast cancer

Received: May 16, 2017     Accepted: August 23, 2017     Published: September 11, 2017

ABSTRACT

Tamoxifen resistance is a serious problem in the endocrine therapy of breast cancer. Long non-coding RNAs play important roles in tumor development. In this study, we revealed the involvement of lncRNA uc.57 and its downstream gene BCL11A in TAM resistance. Tamoxifen-resistant MCF-7R cells showed lower expression of uc.57 and higher expression of BCL11A mRNA and protein than the parental MCF-7 cells. Moreover, levels of uc.57 mRNA were lower and BCL11A mRNA were higher in breast cancer tissues than in precancerous breast tissues. Shikonin treatment reduced tamoxifen resistance in MCF-7R cells both in vitro and in vivo, targeting uc.57/BCL11A. Fluorescence in situ hybridization and RNA immunoprecipitation analyses showed that uc.57 binds to BCL11A. Uc.57 overexpression downregulated BCL11A and reduced tamoxifen resistance in MCF-7R cells both in vitro and in vivo. BCL11A knockdown also reduced tamoxifen resistance by inhibiting PI3K/AKT and MAPK signaling pathways. It thus appears shikonin reduces tamoxifen resistance of MCF-7R breast cancer cells by inducing uc.57, which downregulates BCL11A to inhibit PI3K/AKT and MAPK signaling pathways.


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