Differential microRNA expression profiles determined by next-generation sequencing in three fulvestrant-resistant human breast cancer cell lines

摘要

Fulvestrant resistance is a major clinical issue in the treatment of endocrine-based breast cancer. MicroRNAs (miRNAs) are known to serve an important role in tumor chemoresistance. In the present study, the association between miRNA expression profiles and fulvestrant resistance was investigated in human breast cancer cell lines. Three fulvestrant-resistant breast cancer cell lines, namely MCF-7-CC, MCF-7-TT and MCF-7-21, were established using the human breast cancer cell line MCF-7 as the parental cell line and fulvestrant as the screening drug in vitro. Next-generation sequencing was used to determine the miRNA expression profiles in these cell lines. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the biological functions of differentially expressed miRNAs. In total, 1,536 miRNAs were detected in all the samples, including 1,240 known miRNAs and 296 predicted miRNAs. It was observed that the differential miRNA expression profiles varied among the three fulvestrant-resistant cell lines (MCF-7-CC, MCF-7-TT and MCF-7-21), and certain differentially expressed miRNAs were only detected in one or two of the cell lines. A total of 257 miRNAs that were differentially expressed between MCF-7-CC and MCF-7 cells were detected, among which 69 miRNAs were upregulated and 188 miRNAs were downregulated. In addition, 270 miRNAs with significantly different expression between MCF-7-TT and MCF-7 cells were observed, including 180 upregulated and 90 downregulated miRNAs. Between MCF-7-21 and MCF-7 cells, a total of 227 miRNAs were differentially expressed, among which 52 miRNAs were upregulated and 175 miRNAs were downregulated. The miRNAs that were differentially expressed in the three fulvestrant-resistant cell lines as compared with the parental MCF-7 cell line were primarily involved in the following biological processes: Biological regulation, extracellular matrix-receptor interaction, the Notch signaling pathway and focal adhesion. Taken together, the results suggested that miR-143, miR-145, miR-137, miR-424 and miR-21 may serve important roles in fulvestrant resistance in breast cancer. The study findings may provide a basis for further research on the treatment of fulvestrant-resistant breast cancer.