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

Sun,Xin; Qin,Sida; Fan,Chong; Xu,Chongwen; Du,Ning; Ren,Hong

doi:10.3892/or.2013.2330

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

Authors:
- Xin Sun
- Sida Qin
- Chong Fan
- Chongwen Xu
- Ning Du
- Hong Ren
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Affiliations: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China
Published online on: March 6, 2013 https://doi.org/10.3892/or.2013.2330
Pages: 2079-2087

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Abstract

The oncogenic role of estrogen receptor (ER)α 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 ERα 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, ERα 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, ERα and ERα downstream genes suggested that let-7 acts as a tumor suppressor by inhibiting ERα-mediated cellular malignant growth in ER-positive breast cancer stem cells. The suppression of ERα 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.

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