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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Identification of differentially expressed microRNAs in human male breast cancer
Ulrich Lehmann1, Thomas Streichert, Benjamin Otto
1Institute of Pathology, Medizinische Hochschule Hannover, D-30625 Hannover, Germany. Lehmann.Ulrich@MH-Hannover.de
Background:
The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases.
Methods:
The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods.Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer.
Results:
Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer.
Conclusions:
Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.
Insights
Male breast cancer shows distinct microRNA expression patterns compared to normal tissue. Some microRNAs are uniquely altered in male breast cancer, differing from female breast cancer profiles.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs with crucial roles in cancer biology.
- Expression patterns of miRNAs are altered in various cancers, acting as oncogenes or tumor suppressors.
- While extensively studied in female breast cancer, miRNA expression in male breast cancer remains largely unknown.
Purpose of the Study:
- To investigate and characterize microRNA expression profiles in human male breast cancer.
- To identify specific microRNAs that are differentially expressed in male breast tumors.
Main Methods:
- Analysis of 319 microRNAs in 9 male breast tumors and 15 gynecomastia specimens using bead technology.
- Differential expression analysis via cluster analysis and statistical methods.
- Validation of key microRNAs using real-time PCR in independent cohorts.
Main Results:
- Unsupervised clustering clearly distinguished male breast cancer from control specimens based on miRNA expression.
- Identified significantly up-regulated miRNAs: miR-21, miR-519d, miR-183, miR-197, and miR-493-5p.
- Identified significantly down-regulated miRNAs: miR-145 and miR-497.
Conclusions:
- Male breast cancer exhibits distinct differentially expressed microRNAs.
- Some of these miRNA alterations are specific to male breast cancer and not observed in female breast cancer.
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