A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer

被引：22

作者：

Huang, Peide ^{[1
]}

Li, Fengyu ^{[2
]}

Mo, Zongchao ^{[2
]}

Geng, Chunyu ^{[3
]}

Wen, Fang ^{[3
]}

Zhang, Chunyan ^{[3
]}

Guo, Jia ^{[1
]}

Wu, Song ^{[4
]}

Li, Lin ^{[2
,5
]}

Brunner, Nils ^{[6
]}

Stenvang, Jan ^{[6
]}

机构：

[1] BGI Shenzhen, BGI, Shenzhen, Peoples R China

[2] BGI Shenzhen, BGI Genom, Shenzhen, Peoples R China

[3] BGI Shenzhen, MGI, Shenzhen, Peoples R China

[4] Shenzhen Univ, Affiliated Luohu Hosp, Shenzhen Luohu Hosp Grp, Shenzhen, Peoples R China

[5] Shanghai Jiao Tong Univ, Natl Res Ctr Translat Med, Natl Key Sci Infrastruct Translat Med, Shanghai, Peoples R China

[6] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

基金：

中国国家自然科学基金;

关键词：

breast cancer; docetaxel resistance; RNA sequencing; circRNA; miRNA;

D O I：

10.3389/fonc.2021.669270

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To investigate the relationship between non-coding RNAs [especially circular RNAs (circRNAs)] and docetaxel resistance in breast cancer, and to find potential predictive biomarkers for taxane-containing therapies, we have performed transcriptome and microRNA (miRNA) sequencing for two established docetaxel-resistant breast cancer (DRBC) cell lines and their docetaxel-sensitive parental cell lines. Our analyses revealed differences between circRNA signatures in the docetaxel-resistant and -sensitive breast cancer cells, and discovered circRNAs generated by multidrug-resistance genes in taxane-resistant cancer cells. In DRBC cells, circABCB1 was identified and validated as a circRNA that is strongly up-regulated, whereas circEPHA3.1 and circEPHA3.2 are strongly down-regulated. Furthermore, we investigated the potential functions of these circRNAs by bioinformatics analysis, and miRNA analysis was performed to uncover potential interactions between circRNAs and miRNAs. Our data showed that circABCB1, circEPHA3.1 and circEPHA3.2 may sponge up eight significantly differentially expressed miRNAs that are associated with chemotherapy and contribute to docetaxel resistance via the PI3K-Akt and AGE-RAGE signaling pathways. We also integrated differential expression data of mRNA, long non-coding RNA, circRNA, and miRNA to gain a global profile of multi-level RNA changes in DRBC cells, and compared them with changes in DNA copy numbers in the same cell lines. We found that Chromosome 7 q21.12-q21.2 was a common region dominated by multi-level RNA overexpression and DNA amplification, indicating that overexpression of the RNA molecules transcribed from this region may result from DNA amplification during stepwise exposure to docetaxel. These findings may help to further our understanding of the mechanisms underlying docetaxel resistance in breast cancer.

引用

页数：14

共 72 条

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