Breast Cancer Research and Treatment

, Volume 127, Issue 1, pp 69–80

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

  • Yingchun Zhao
  • Caishu Deng
  • Jiarui Wang
  • Jing Xiao
  • Zoran Gatalica
  • Robert R. Recker
  • Gary Guishan Xiao
Preclinical study

DOI: 10.1007/s10549-010-0972-2

Cite this article as:
Zhao, Y., Deng, C., Wang, J. et al. Breast Cancer Res Treat (2011) 127: 69. doi:10.1007/s10549-010-0972-2

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.

Keywords

Let-7 family microRNAs Breast cancer FFPE Estrogen receptor-α signaling 

Abbreviations

ANOVA

Analysis of variance

BT-IC

Breast tumor-initiating cells

DCIS

Ductal carcinoma in situ

DMSO

Dimethyl sulfoxide

E2

17-β-Estradiol

ER

Estrogen receptor

ER-α

ER alpha

ERE

Estrogen response element

FBS

Fetal bovine serum

FFPE

Formalin-fixed paraffin-embedded

IDC

Invasive ductal carcinoma

miRNA

microRNA

MTT

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

3′-UTR

3′-Untranslated region

Supplementary material

10549_2010_972_MOESM1_ESM.xls (24 kb)
Supplementary material 1 (XLS 24 kb)
10549_2010_972_MOESM2_ESM.doc (250 kb)
Supplementary material 2 (DOC 250 kb)

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Yingchun Zhao
    • 1
  • Caishu Deng
    • 2
  • Jiarui Wang
    • 1
  • Jing Xiao
    • 1
  • Zoran Gatalica
    • 2
  • Robert R. Recker
    • 1
  • Gary Guishan Xiao
    • 1
  1. 1.Genomics & Functional Proteomics Laboratories, Osteoporosis Research CenterCreighton University Medical CenterOmahaUSA
  2. 2.Department of PathologyCreighton University Medical CenterOmahaUSA