Differential microRNA profiles between fulvestrant-resistant and tamoxifen-resistant human breast cancer cells

Abstract

Increasing evidence has shown that the dysregulation of microRNAs (miRNAs) is associated with drug resistance. Fulvestrant and tamoxifen represent the major endocrine drugs for the treatment of breast cancer patients, and yet little is known about the biological mechanisms of acquiring resistance to fulvestrant and tamoxifen, let alone the differences between cell lines resistant to these two drugs. Exploration of the differential miRNA profiles between these two cell lines is a useful way to further clarify these resistance mechanisms. The fulvestrant-resistant cell line (MCF7-F) and the tamoxifen-resistant cell line (MCF7-T) were established from the drug-sensitive parental MCF7 cell line using a 21-day high-dose antiestrogen induction method. Differentially expressed miRNA profiles of MCF7-F and MCF7-T were detected using microarray; then, multiple bioinformatic analyses were carried out, including protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Compared with the parental MCF7 cell line, more miRNAs were found to be participating in the process of acquiring fulvestrant resistance than tamoxifen resistance. miR-4532, miR-486-5p, miR-138, miR-1228, and miR-3178 could be new targets for combating both fulvestrant resistance and tamoxifen resistance. miR-3188, miR-21, miR-149, and others may be associated with fulvestrant resistance, whereas miR-342 and miR-1226 may be associated with tamoxifen resistance in breast cancer cells. We found differential miRNA profiles between fulvestrant-resistant and tamoxifen-resistant breast cancer cells, but the definite mechanism involved in gaining resistance still needs further study.