lncRNA profile study reveals the mRNAs and lncRNAs associated with docetaxel resistance in breast cancer cells

被引:50
作者
Huang, Peide [1 ,3 ,4 ]
Li, Fengyu [3 ]
Li, Lin [3 ]
You, Yuling [3 ]
Luo, Shizhi [3 ]
Dong, Zhensheng [3 ]
Gao, Qiang [3 ]
Wu, Song [2 ]
Brunner, Nils [1 ]
Stenvang, Jan [1 ]
机构
[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Sect Pharmacotherapy, DK-2200 Copenhagen N, Denmark
[2] Shenzhen Univ, Affiliated Luohu Hosp, Shenzhen Luohu Hosp Grp, Shenzhen, Peoples R China
[3] BGI Shenzhen, BGI Genom, Shenzhen 518083, Peoples R China
[4] Shenzhen Univ, Affiliated Hosp 1, Shenzhen, Peoples R China
基金
中国国家自然科学基金;
关键词
LONG NONCODING RNAS; GENE-EXPRESSION; MESENCHYMAL TRANSITION; SIGNALING PATHWAY; ABCB1; EXPRESSION; DRUG-RESISTANCE; P-GLYCOPROTEIN; UP-REGULATION; DOXORUBICIN; PACLITAXEL;
D O I
10.1038/s41598-018-36231-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Resistance to adjuvant systemic treatment, including taxanes (docetaxel and paclitaxel) is a major clinical problem for breast cancer patients. lncRNAs (long non-coding RNAs) are non-coding transcripts, which have recently emerged as important players in a variety of biological processes, including cancer development and chemotherapy resistance. However, the contribution of lncRNAs to docetaxel resistance in breast cancer and the relationship between lncRNAs and taxane-resistance genes are still unclear. Here, we performed comprehensive RNA sequencing and analyses on two docetaxel-resistant breast cancer cell lines (MCF7-RES and MDA-RES) and their docetaxel-sensitive parental cell lines. We identified protein coding genes and pathways that may contribute to docetaxel resistance. More importantly, we identified lncRNAs that were consistently up-regulated or down-regulated in both the MCF7-RES and MDA-RES cells. The co-expression network and location analyses pinpointed four overexpressed lncRNAs located within or near the ABCB1 (ATP-binding cassette subfamily B member 1) locus, which might up-regulate the expression of ABCB1. We also identified the lncRNA EPB41L4A-AS2 (EPB41L4A Antisense RNA 2) as a potential biomarker for docetaxel sensitivity. These findings have improved our understanding of the mechanisms underlying docetaxel resistance in breast cancer and have provided potential biomarkers to predict the response to docetaxel in breast cancer patients.
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页数:15
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