Lee Chia-Hsien, Kuo Wen-Hong, Lin Chen-Ching, Oyang Yen-Jen, Huang Hsuan-Cheng, Juan Hsueh-Fen
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106, Taiwan.
Int J Mol Sci. 2013 May 30;14(6):11560-606. doi: 10.3390/ijms140611560.
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.
微小RNA是一类内源性小RNA调节因子，与多种癌症相关。乳腺癌是全球女性面临的主要健康威胁。许多微小RNA被报道与乳腺癌的进展和致癌作用有关。在本研究中，我们旨在发现新的乳腺癌相关微小RNA并阐明其功能。首先，我们通过整合微小RNA靶标预测数据库的数据以及微小RNA和信使核糖核酸的表达谱来确定可靠的微小RNA-靶标对。然后，利用可靠的配对以及人类蛋白质参考数据库（HPRD）中的已知相互作用数据构建微小RNA调节的蛋白质相互作用网络（PIN）。最后，通过功能富集分析阐明微小RNA调节的PIN的功能。从结果中，我们确定了一些先前报道的与乳腺癌相关的微小RNA以及PIN的功能，例如miR-125b、miR-125a、miR-21和miR-497。还发现了一些与乳腺癌无已知关联的新微小RNA，并阐明了其PIN的推定功能。这些包括miR-139和miR-383。此外，我们通过使用我们的微小RNA表达谱数据进行受试者工作特征（ROC）曲线分析、基于基因表达的乳腺癌在线生存分析（GOBO）以及文献检索来验证我们的结果。我们的结果可能为乳腺癌相关微小RNA的研究提供新的见解。
