Let-7: A regulator of the ERα signaling pathway in human breast tumors and breast cancer stem cells

The oncogenic role of estrogen receptor (ER)alpha and its correlation with let-7 microRNAs (miRNAs) have been studied and confirmed in breast tumors; however, this correlation has not been investigated in breast cancer stem cells (BCSCs). In the present study, we detected the expression of let-7 and ER alpha in ER-positive breast tumor tissues. Furthermore, we used a FACSAria cell sorter to separate side population (SP) cells from the MCF-7 and T47-D cell lines by Hoechst 33342 staining. The expression of let-7 miRNAs, ER alpha and its downstream genes in SP and non-SP (NSP) cells were analyzed. In additional experiments, we transfected a plasmid expressing let-7a into SP cells isolated from the MCF-7 and T47-D cell lines in order to observe changes in the expression of downstream genes (cyclin D1 and pS2). The correlation among let-7, ER alpha and ER alpha downstream genes suggested that let-7 acts as a tumor suppressor by inhibiting ER alpha-mediated cellular malignant growth in ER-positive breast cancer stem cells. The suppression of ER alpha by the upregulation of let-7 expression may be a promising strategy for the inhibition of the ER signaling pathway and for the elimination of cancer stem cells, thus aiding in the treatment of breast cancer.