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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalBreast Cancer Research and Treatment
Volume127
Issue number1
DOIs
StatePublished - May 2011

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Estrogen Receptor alpha
MicroRNAs
Estrogen Receptors
Breast Neoplasms
Ductal Carcinoma
Carcinoma, Intraductal, Noninfiltrating
MCF-7 Cells
Paraffin
Formaldehyde
3' Untranslated Regions
Computational Biology
Luciferases
Carcinogenesis
Breast
Cell Proliferation
RNA
Cell Line
Messenger RNA
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer. / Zhao, Yingchun; Deng, Caishu; Wang, Jiarui; Xiao, Jing; Gatalica, Zoran; Recker, Robert R.; Xiao, Gary Guishan.

In: Breast Cancer Research and Treatment, Vol. 127, No. 1, 05.2011, p. 69-80.

Research output: Contribution to journalArticle

Zhao, Yingchun ; Deng, Caishu ; Wang, Jiarui ; Xiao, Jing ; Gatalica, Zoran ; Recker, Robert R. ; Xiao, Gary Guishan. / Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer. In: Breast Cancer Research and Treatment. 2011 ; Vol. 127, No. 1. pp. 69-80.
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