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

• Type of Material: Article
• Authors: Baotong Zhang, Nankai University; Ranran Zhao, Nankai University; Yuan He, Nankai University; Xing Fu, Nankai University; Liya Fu, Nankai University; Zhengmao Zhu, Nankai University; Li Fu, Tianjin Medical University; Jin-Tang Dong, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Zhang et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.6790
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 7
• Issue: 5
• Start Page: 5702
• End Page: 5714
• Grant/Funding Information: This work was supported by grant 31171250 from the National Natural Science Foundation of China.
• Keywords: breast cancer; miR-100; luminal A subtype; paclitaxel; mTOR
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology; Biology, Cell

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.