Oncotarget

Research Papers:

Micro RNA 100 sensitizes luminal A breast cancer cells to paclitaxel treatment in part by targeting mTOR

Baotong Zhang, Ranran Zhao, Yuan He, Xing Fu, Liya Fu, Zhengmao Zhu, Li Fu and Jin-Tang Dong _

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Oncotarget. 2016; 7:5702-5714. https://doi.org/10.18632/oncotarget.6790

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Abstract

Baotong Zhang1,2,*, Ranran Zhao1,*, Yuan He1, Xing Fu1, Liya Fu1, Zhengmao Zhu1, Li Fu3 and Jin-Tang Dong1,2

1 Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China

2 Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA

3 Cancer Hospital of Tianjin Medical University, Tianjin, China

* These authors have contributed equally to this work

Correspondence to:

Jin-Tang Dong, email:

Keywords: miR-100, paclitaxel, mTOR, breast cancer, luminal A subtype

Received: October 01, 2015 Accepted: December 23, 2015 Published: December 29, 2015

Abstract

Luminal A breast cancer usually responds to hormonal therapies but does not benefit from chemotherapies, including microtubule-targeted paclitaxel. MicroRNAs could play a role in mediating this differential response. In this study, we examined the role of micro RNA 100 (miR-100) in the sensitivity of breast cancer to paclitaxel treatment. We found that while miR-100 was downregulated in both human breast cancer primary tumors and cell lines, the degree of downregulation was greater in the luminal A subtype than in other subtypes. The IC50 of paclitaxel was much higher in luminal A than in basal-like breast cancer cell lines. Ectopic miR-100 expression in the MCF-7 luminal A cell line enhanced the effect of paclitaxel on cell cycle arrest, multinucleation, and apoptosis, while knockdown of miR-100 in the MDA-MB-231 basal-like line compromised these effects. Similarly, overexpression of miR-100 enhanced the effects of paclitaxel on tumorigenesis in MCF-7 cells. Rapamycin-mediated inhibition of the mammalian target of rapamycin (mTOR), a target of miR-100, also sensitized MCF-7 cells to paclitaxel. Gene set enrichment analysis showed that genes that are part of the known paclitaxel-sensitive signature had a significant expression correlation with miR-100 in breast cancer samples. In addition, patients with lower levels of miR-100 expression had worse overall survival. These results suggest that miR-100 plays a causal role in determining the sensitivity of breast cancers to paclitaxel treatment.


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