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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-06-10

AUTHORS

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

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. More... »

PAGES

69-80

References to SciGraph publications

  • 2009-08-17. Protein lysate microarray analysis to identify microRNAs regulating estrogen receptor signaling in breast cancer cell lines in ONCOGENE
  • 2006-06-19. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies in MOLECULAR CANCER
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  • 2007-09-26. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer in NATURE
  • 2007-10-08. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype in GENOME BIOLOGY
  • 2009-03-16. Robust global micro-RNA profiling with formalin-fixed paraffin-embedded breast cancer tissues in LABORATORY INVESTIGATION
  • 2008-10-06. MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death in ONCOGENE
  • 2000-11. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA in NATURE
  • 2008-02-12. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis in CELL RESEARCH
  • 1971-12. Oestradiol Receptors in Carcinoma and Benign Disease of the Breast: An In Vitro Assay in BRITISH JOURNAL OF CANCER
  • 2010-03-05. EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast in MODERN PATHOLOGY
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    URI

    http://scigraph.springernature.com/pub.10.1007/s10549-010-0972-2

    DOI

    http://dx.doi.org/10.1007/s10549-010-0972-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1011222673

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20535543


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