Abstract
MicroRNAs, which are small endogenous RNA regulators, have been associated with various types of cancer. Breast cancer is a major health threat for women worldwide. Many miRNAs were reported to be associated with the progression and carcinogenesis of breast cancer. In this study, we aimed to discover novel breast cancer-related miRNAs and to elucidate their functions. First, we identified confident miRNA-target pairs by combining data from miRNA target prediction databases and expression profiles of miRNA and mRNA. Then, miRNA-regulated protein interaction networks (PINs) were constructed with confident pairs and known interaction data in the human protein reference database (HPRD). Finally, the functions of miRNA-regulated PINs were elucidated by functional enrichment analysis. From the results, we identified some previously reported breast cancer-related miRNAs and functions of the PINs, e.g., miR-125b, miR-125a, miR-21, and miR-497. Some novel miRNAs without known association to breast cancer were also found, and the putative functions of their PINs were also elucidated. These include miR-139 and miR-383. Furthermore, we validated our results by receiver operating characteristic (ROC) curve analysis using our miRNA expression profile data, gene expression-based outcome for breast cancer online (GOBO) survival analysis, and a literature search. Our results may provide new insights for research in breast cancer-associated miRNAs.
Highlights
Breast cancer is a global health threat for women
From the results of significance analysis of microarrays (SAM) analysis, we identified some well-known breast cancer-related miRNAs (Table S1)
The nerve growth factor receptor pathway was enriched in miR-regulated protein interaction networks (PINs) of miR-520d-3p, miR-497-5p, miR-125a-5p, miR-125b-5p, and miR-31-5p, and the epidermal growth factor receptor pathway was enriched in miR-regulated PINs of miR-520d-3p, miR-21-5p, and miR-497-5p
Summary
Breast cancer is a global health threat for women. According to a 2008 survey [1], breast cancer was the leading cause of cancer deaths in women. Our knowledge of possible risk factors has led to developments in diagnostic methods, drugs, and surgery procedures for treatment [2,3]; the details of breast carcinoma progression, and perhaps most importantly, how to cure breast cancer, remain elusive. Previous research has identified a number of risk factors for breast cancer. Late menopause, obesity, late first full pregnancy, and hormone replacement therapy were considered as high risk factors for breast cancer [2]. Breast cancer risk has been reported to be related to fat intake in diets rich in red meats and high-fat dairy foods [3]
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