Differential expression and androgen regulation of microRNAs and metalloprotease 13 in breast cancer cells

MicroRNA molecules (miRNAs) play important roles in regulating cell behavior. The expression of certain miRNAs has been shown to be regulated by the androgen receptor (AR), which seems to have a critical role in the tumorigenic process of breast cancer. The differential expression of 84 miRNAs was first examined in three breast cancer cell lines: the luminal MCF-7 and T47D cells and the molecular apocrine MDA-MB-453 cells. Analysis of basal expression of miRNAs revealed that each cell line had distinct miRNA expression where let-7a and -7b were markers of MDA-MB-453 cells, whereas miR-205 was a marker for the luminal cell lines. Treating the cells with the AR agonist, CI-4AS-1, resulted in unique alterations in the expression of specific miRNA among the three cell lines. Particularly, the expression of miR-100 and miR-125 was reduced in MDA-MB-453 cells by five and three folds, respectively. This effect was simultaneous with AR-induced increase in the expression and extracellular release of metalloprotease-13 (MMP13). Transfection of cells with either miR-100 or miR-125b negated the induction of MMP13 release. Additionally, AR activation induced a morphological alteration of MDA-MB-453 cells, which was blocked by miR-125b only. Collectively, these data indicate that AR may control the biological behavior of breast cancer cells and protein expression via miRNAs.