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

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.

• Authors: Yingchun Zhao, Caishu Deng, Jiarui Wang, Jing Xiao, Zoran Gatalica, Robert R Recker, Gary Guishan Xiao
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 127 Issue 1 Pg. 69-80 (May 2011) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 20535543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• MicroRNAs
• mirnlet7 microRNA, human

Topics

• Apoptosis (genetics)
• Base Sequence
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Estrogen Receptor alpha (metabolism)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics, metabolism)
• Signal Transduction