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Breast Cancer Res Treat. 2011 May;127(1):69-80. doi: 10.1007/s10549-010-0972-2. Epub 2010 Jun 10.

Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer.

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1
Genomics & Functional Proteomics Laboratories, Osteoporosis Research Center, Creighton University Medical Center, 601 N 30th ST, Suite 6730, Omaha, NE 68131, USA.

Abstract

In order to understand how microRNAs (miRNAs) regulate breast cancer tumorigenesis, a miRNA expression microarray screening was performed using RNA from formalin-fixed paraffin-embedded (FFPE) breast tissues, which included benign (n = 13), ductal carcinoma in situ (DCIS) (n = 16), and invasive ductal carcinoma (IDC) (n = 15). Twenty-five differentially expressed miRNAs (P < 0.01) were identified, of which let-7 family miRNAs were down-regulated in human breast cancer tissues at stages of DCIS and IDC compared to benign stage. We further found that there was an inverse correlation between ER-α expression and several members of let-7 family in the FFPE tissues. Next, we performed bioinformatics analysis and found that let-7 miRNA sequences match sequence in the 3'-UTR of estrogen receptor alpha (ER-α), suggesting ER-α may be a target of let-7, which was further confirmed by a number of experimental assays, including luciferase assay, protein expression, and mRNA expression. Overexpression of let-7 miRNAs in ER-positive breast cancer MCF7 cell line negatively affected ER-α activity. As expected, dampening of the ER-α signaling by let-7 miRNAs inhibited cell proliferation, and subsequently triggered the cell apoptotic process in MCF7 cells. In conclusion, our findings indicate a new regulatory mechanism of let-7 miRNAs in ER-α mediated cellular malignant growth of breast cancer.

PMID:
20535543
DOI:
10.1007/s10549-010-0972-2
[Indexed for MEDLINE]

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