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

Abstract

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.

MicroRNAs and Androgen Receptor: Emerging Players in Breast Cancer

“…Furthermore, treatment with the AR agonist CI-4AS-1 led to alterations in the expression profile of other micro-RNAs, such as miR-100 and miR-125 which were found significantly downregulated simultaneously with the increase and extracellular release of metalloprotease-13 (MMP13). Interestingly, the transfection of miR-100 and -125b abrogated the induction of MMP13, suggesting a correlation between these micro-RNAs and AR in the control of BC growth (Ahram et al, 2017). In TNBC, the gene SRY-box 4 ( Sox4 ) is known to promote EMT, thereby progression, invasion and metastasis, and is found abnormally overexpressed.…”

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“…The development of biology is helpful in finding therapeutic targets for diseases [27]. Biomedicine has made great progress in cancer treatment [28].…”

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

“…Similarly, miR-100 and miR-125 expression is negatively correlated with AR in BC progression. Indeed, the downregulation of both miRNAs are linked to the extracellular release of metalloprotease-13 (MMP13), which is inhibited by transient expression of miR-100 and miR-125, also reversing the BC progression by AR [60]. AR negatively induces lncRNA in the progression of triple-negative breast cancer (TNBC).…”