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 journalArticlepeer-review

97 Scopus citations

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 (US)
Pages (from-to)69-80
Number of pages12
JournalBreast Cancer Research and Treatment
Volume127
Issue number1
DOIs
StatePublished - May 1 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer'. Together they form a unique fingerprint.

Cite this