Oncotarget

Research Papers:

LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer

Sheng-Jia Shi, Li-Juan Wang, Bo Yu, Yun-Hui Li, Yong Jin and Xiao-Zhong Bai _

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Oncotarget. 2015; 6:11652-11663. https://doi.org/10.18632/oncotarget.3457

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Abstract

Sheng-Jia Shi1,*, Li-Juan Wang2,*, Bo Yu1, Yun-Hui Li1, Yong Jin1, Xiao-Zhong Bai1

1Department of Administration and Department of Aristogenesis, No. 202 Hospital of PLA, No. 5, Shenyang, 110003, Liaoning Province, P.R. China

2Department of Oncology, the First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Xiao-Zhong Bai, e-mail: [email protected]

Keywords: lnc-ATB, trastuzumab resistance, EMT, TGF-β, breast cancer

Received: February 05, 2015     Accepted: February 25, 2015     Published: March 23, 2015

ABSTRACT

Trastuzumab resistance is leading cause of mortality in HER2-positive breast cancers, and the role of TGF-β-induced epithelial-mesenchymal transition (EMT) in trastuzumab resistance is well established, but the involvement of lncRNAs in trastuzumab resistance is still unknown. Here, we generated trastuzumab-resistant breast cancer cells with increased invasiveness compared with parental cells, and observed robust epithelial–mesenchymal transition (EMT) and consistently elevated TGF-β signaling in these cells. We identified long noncoding RNA activated by TGF-β (lnc-ATB) was the most remarkably upregulated lncRNA in TR SKBR-3 cells and the tissues of TR breast cancer patients. We found that lnc-ATB could promote trastuzumab resistance and invasion-metastasis cascade in breast cancer by competitively biding miR-200c, up-regulating ZEB1 and ZNF-217, and then inducing EMT. In addition, we also found that the high level of lnc-ATB was correlated with trastuzumab resistance of breast cancer patients. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-β signaling, could predispose breast cancer patients to EMT and trastuzumab resistance.


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