Let-7 microRNA: tumour suppression activity in breast cancer


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Yezi Xerri, Mark N Evans, Giorgio Inoue, Tennent K Hanley, Douglas L Hainz*
Author Affiliations
∗Correspondence author e-mail: Douglas.Hainz@asobm.org: 1Division of Biochemistry, Loma Linda University, Mortensen, USA

 

Abstract

Breast cancer is the most prevalent malignancy among women, with an estimated 290,000 new cases diagnosed in the United States in 2014. It is classified into distinct molecular subtypes with divergent therapeutic and prognostic implications. Triple negative breast cancer (TNBC) is classified as estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and HER2-negative (HER2-). TNBC is associated with the most aggressive disease course, a lack of targeted therapies, and the worst prognosis. Novel therapeutic approaches are urgently needed to suppress the growth and dissemination of TNBC. MicroRNAs (miRNAs or miRs) are short, noncoding RNAs that post-transcriptionally regulate the expression of genes by binding to complementary sequences on their target mRNAs. MiRNAs are key regulators of cellular processes including development, differentiation, apoptosis, metabolism, and proliferation. A growing body of evidence indicates that miRNAs are critically involved in the development and progression of breast cancer. In human breast cancer specimens, some miRNAs, such as the let-7 family, are found to be downregulated, while others like miR-21 are upregulated. MiRNAs that are downregulated in breast cancer are referred to as tumor-suppressive miRNAs and those that are upregulated are referred to as oncogenic miRNAs. The let-7 family of miRNAs is one of the first clusters of miRNAs to be discovered. In mammals, the let-7 family has been shown to comprise at least nine mature members: let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, let-7i, and miR-98. The dysregulation of the let-7 family of miRNAs is implicated in several types of cancer, including lung cancer, ovarian cancer, colorectal cancer, liver cancer, and breast cancer. However, the tumor suppression activity of the let-7 family of miRNAs in breast cancer remains largely unknown. MCF-7 and MDA-MB-231 breast cancer cell lines are commonly used to study the mechanisms of hormone action. MCF-7 cells, an ER+ breast cancer cell line, are noninvasive and have a low initiation rate of metastasis. In contrast, MDA-MB-231 cells, classified as a basal subtype, are highly invasive and form metastases in distant organs.

Keywords: Breast cancer; Let-7; mRNA; Xenograft; qRT-PCR

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.

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Research Article


DOI: http://dx.doi.org/10.18081/2333-5106/015-02/389-399
American Journal of BioMedicine 2015, Volume 3, Issue 2, pages 83–99
Received November 13, 2014; Accepted March; 11, 2015, Published April 30, 2015

How to cite this article
Xerri Y, Evans MN, Inoue G, Hanley TK, Hainz DL. Let-7 microRNA: tumor suppression activity in breast cancer. American Journal of BioMedicine 2015;3(2):89–99
Review Article
1. Abstract
2. Keywords
3. Introduction
5. Results
6. Discussion
7. References

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