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.
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机译：据报道，微小RNA（miRNA / miRs）与各种类型人类癌症的发生和发展有关。但是，这种关联的潜在机制仍不清楚。本研究的目的是基于乳头溢流中的miRNA表达谱，利用生物信息学分析来探索miRNA在乳腺癌发展中的潜在功能。先前的研究表明，与乳腺良性病变患者相比，乳腺癌患者的乳头溢液中miR-3646和miR-4484的上调以及miR-4732-5p的下调。在本研究中，使用TargetScan和MicroRNA Target Prediction and Functional Study Database预测了miR-3646，−4484和−4732-5p的靶基因。通过基因本体术语富集分析，京都基因百科全书和基因组途径富集分析和蛋白质-蛋白质相互作用分析，进一步分析了预测的目标基因。包括ADIPOQ，CPEB1，DNAJB4，EIF4E，APP和BCLAF1在内的许多与癌相关的基因被证明是miR-3646，−4484和−4732-5p的靶标。生物信息学分析将miR-3646与Rap1和TGF-β信号通路关联，将miR-4484与ErbB，雌激素和粘着斑信号通路关联，并将miR-4732-5p与蛋白聚糖信号通路关联。值得注意的是，蛋白质间相互作用分析确定了这些miRNA的许多预测靶标彼此相关。此外，已确定miRNA的靶基因在许多转录因子（TF）的调控下。已确定miR-3646，−4484和−4732-5p的预测靶基因在与癌症相关的信号通路和TF-mRNA网络中起作用，表明它们在乳腺癌的发生和发展中起作用。这些结果为miR-3646，−4484和−4732-5p的功能和分子机理提供了全面的观点，并将有助于未来的研究。
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