Breast cancer is one of the most common cancers in women worldwide, resulting in over 400,000 deaths per year. MicroRNAs (miRNAs) are a class of non-coding, small RNA molecules, which can play an important role in biological processes by regulating gene expression at the post-transcriptional level. In view of the importance of microRNAs (miRNAs) in breast cancer, a better understanding on the synergistic regulations of miRNAs in breast cancer is of great significance for developing relevant diagnosis and therapy strategies. In this context, this study firstly collected the data on differentially expressed miRNAs (DE-miRNAs) of breast cancer from public database and literature, retrieved the information on predicted target genes of DE-miRNAs from miRecords, and further used ClueGo to perform KEGG functional enrichment analysis. Moreover, the complex synergistic relationships among DEmiRNAs were discussed by constructing miRNA-miRNA functional synergistic network and relevant sub-networks. The results indicate that both up- and downregulated miRNAs play the essential roles in the tumorigenesis of breast cancer. In addition, there are two characteristics of synergistic miRNAs: 1) the synergistic effect is stronger between the same dysregulated miRNAs; 2) the synergistic effect is stronger among miRNA family members than non-family miRNAs. Through this study, some important synergistic miRNAs are also found in the progression of breast cancer. MiR-15 family plays a significant synergistic role in the progression of breast cancer, while there are several key synergistic miRNAs in this process, including miR-203, miR-579, miR-495, and miR-432. These miRNAs are promising for clinical use in breast cancer and are worth of further experimental study.

乳腺癌（Breast Cancer，BC）是全世界婦女中最常見的惡性腫瘤之一，每 年將導致 40 萬的人口死亡。微小 RNA（microRNA）是一類非編碼、小分子 RNA，通過在轉錄后水平調節基因的表達從而在生物學過程中發揮重要作用。 考慮到 miRNAs 在乳腺癌中的重要性，系統地理解 miRNAs 在乳腺癌中的協同 調節作用對於發展相關的診斷和治療策略尤為重要。在本研究中，首先從文獻 及公共數據庫匯總獲取差異表達的 miRNAs，并通過 miRecords 提取差異表達 miRNAs 的預測靶點，然後通過 ClueGo 插件對 miRNAs 的預測靶點進行 KEGG 功能富集，從整體水平上分析 miRNAs 在乳腺癌中的功能。接著，我們通過構 建 miRNA-miRNA 功能協同網絡及其相關子網絡來分析乳腺癌中差異表達 miRNAs 之間複雜的協同關係。結果表明，上調和下調的 miRNAs 都在乳腺癌 的癌變中發揮重要的作用。此外，發現協同作用 miRNAs 之間有兩個重要特點： 1）同一差異表達的 miRNAs 之間具有更強的協同作用；2）miRNA 家族成員之 間的協同作用強於非 miRNA 家族成員。通過本研究，還發現了一些在乳腺癌 的進程中具有重要協同作用的 miRNAs。MiR-15 家族在乳腺癌的進程中佔有重 要的地位，同時其他一些關鍵的協同 miRNAs，如 miR-203、miR-579、miR- 495 和 miR-432 等也在乳腺癌的發生發展中發揮重要的協同作用。這些 miRNAs 對於診斷、預後和治療乳腺癌都具有潛在的臨床應用價值，并值得今後進一步 的實驗研究和驗證。 關鍵詞：乳腺癌，差異表達 miRNAs，miRNA-miRNA 功能協同網絡，協 同調控，miR-15 家族，miR-203