Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer.
Cancer chemoresistance is regulated by complex genetic and epigenetic networks. In this study, the features of gene expression, methylation, and microRNA (miRNA) expression were investigated with high-throughput sequencing in human breast cancer MCF-7 cells resistant to adriamycin (MCF-7/ADM) and paclitaxel (MCF-7/PTX). We found that: ① both of the chemoresistant cell lines had similar, massive changes in gene expression, methylation, and miRNA expression versus chemosensitive controls. ② Pairwise integration of the data highlighted sets of genes that were regulated by either methylation or miRNAs, and sets of miRNAs whose expression was controlled by DNA methylation in chemoresistant cells. ③ By combining the three sets of high-throughput data, we obtained a list of genes whose expression was regulated by both methylation and miRNAs in chemoresistant cells; ④ Expression of these genes was then validated in clinical breast cancer samples to generate a 17-gene signature that showed good predictive and prognostic power in triple-negative breast cancer patients receiving anthracycline-taxane-based neoadjuvant chemotherapy. In conclusion, our results have generated a new workflow for the integrated analysis of the effects of miRNAs and methylation on gene expression during the development of chemoresistance.
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
Dong-Xu
DX
He
Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, PR China.
Feng
F
Gu
Agricultural Genomes Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China.
Fei
F
Gao
State Key Lab of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
Jun-jun
JJ
Hao
Agricultural Genomes Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China.
Desheng
D
Gong
Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
Xiao-Ting
XT
Gu
Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
Ai-Qin
AQ
Mao
Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
Jian
J
Jin
Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, PR China.
Li
L
Fu
Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
Xin
X
Ma
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D015203:Reproducibility of Results; D059467:Transcriptome
D035683:MicroRNAs