Bioinformatics analysis of dysregulated microRNAs in the nipple discharge of patients with breast cancer

MicroRNAs (miRNAs/miRs) have been reported to be associated with the tumorigenesis and progression of various types of human cancer; however, the underlying mechanisms of this association remain unclear. The aim of the present study was to explore the potential functions of miRNAs in the development of breast cancer using bioinformatics analysis, based on the miRNA expression profile in nipple discharge. A previous study demonstrated the upregulation of miR-3646 and miR-4484, and the downregulation of miR-4732-5p in the nipple discharge of patients with breast cancer, compared with patients with benign breast lesions. In the present study, the target genes of miR-3646, −4484 and −4732-5p were predicted using TargetScan and the MicroRNA Target Prediction and Functional Study Database. The predicted target genes were further analyzed by Gene Ontology term enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and protein-protein interaction analysis. Numerous carcinoma-associated genes, including ADIPOQ, CPEB1, DNAJB4, EIF4E, APP and BCLAF1, were revealed to be putative targets of miR-3646, −4484 and −4732-5p. Bioinformatics analysis associated miR-3646 with the Rap1 and TGF-β signaling pathways, miR-4484 with the ErbB, estrogen and focal adhesion signaling pathways, and miR-4732-5p with the proteoglycan signaling pathway. Notably, protein-protein interaction analysis identified that numerous predicted targets of these miRNAs were associated with one other. In addition, the target genes of the miRNAs were identified to be under the regulation of a number of transcription factors (TFs). The predicted target genes of miR-3646, −4484 and −4732-5p were identified to serve a role in cancer-associated signaling pathways and TF-mRNA networks, indicating that they serve a role in breast carcinogenesis and progression. These results provide a comprehensive view of the functions and molecular mechanisms of miR-3646, −4484 and −4732-5p, and will aid in future studies.