In view of the importance of microRNAs (miRNAs) in breast cancer, it is of great significance to provide a better understanding on the synergistic regulations of miRNAs in breast cancer for developing relevant diagnosis and therapy strategies. We collected the differentially expressed miRNAs (DE-miRNAs) in breast cancer from public databases and literatures, retrieved the predicted target genes of DE-miRNAs from miRecords, and further used ClueGO to perform KEGG functional enrichment analysis. Moreover, the complex synergistic relationships among DE-miRNAs were demonstrated by constructing miRNA-miRNA functional synergistic networks and sub-networks. The results indicate that both up- and down-regulated miRNAs play essential roles in the tumorigenesis, progression, metastasis, angiogenesis, and/or immune escaping of breast cancer. Furthermore, we found that the synergistic effect is stronger among miRNA family members than non-family miRNAs. The miR-15 family, miR-203, miR-579, miR-495, and miR-432, play a significant synergistic role in the initiation and development of breast cancer. These findings might provide new insights in understanding the mechanisms of breast tumorigenesis mediated by miRNAs, as well as contribute to the diagnosis and treatment of breast cancer. © 2017 Association for Computing Machinery.
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