Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Yingchun Zhao Caishu Deng Jiarui Wang Jing Xiao Zoran Gatalica Robert R. Recker Gary Guishan Xiao
- چاپ و سال / کشور: 2010
Description
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-a 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 30-UTR of estrogen receptor alpha (ER-a), suggesting ER-a 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-a activity. As expected, dampening of the ER-a 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-a mediated cellular malignant growth of breast cancer.
Breast Cancer Res Treat (2011) 127:69–80 Received: 10 March 2010 / Accepted: 26 May 2010 / Published online: 10 June 2010 Springer Science+Business Media, LLC. 2010
