It is crucial to identify novel molecular biomarkers and therapeutic targets for triple-negative breast cancer (TNBC). The androgen receptor (AR) is a regulator of TNBC, acting partially via microRNA molecules (miRNAs). In this study, we used PCR arrays to profile the expression of 84 miRNAs in 24 TNBC tissue samples, which were equally classified according to AR expression and/or metastasis. Several bioinformatics tools were then utilized to determine the potentially affected protein targets and signaling pathways. Seven miRNAs were found to be significantly more highly expressed in association with AR expression, including miR-328-3p and miR-489-3p. Increased expression of miR-205-3p was found to be significantly associated with metastasis. Certain miRNAs were specifically found to be differentially expressed in either metastatic or non-metastatic AR-positive tumors. A gene ontology (GO) analysis indicated biological roles in the regulation of transcription, cellular response to DNA damage, and the transforming growth factor-beta (TGF-beta) signaling pathway. The GO analysis also showed enrichment in kinase and transcription factor activities. The TGF-beta and a number of kinase-dependent pathways were also retrieved using the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. This study offers an understanding of the role of AR in TNBC and further implicates miRNAs in mediating the effects of AR on TNBC.
识别三阴性乳腺癌（TNBC）的新型分子生物标志物和治疗靶点至关重要。雄激素受体（AR）作为TNBC的调控因子，其作用部分通过微小RNA分子（miRNA）介导。本研究采用PCR阵列技术，对24例TNBC组织样本中84种miRNA的表达谱进行分析，这些样本根据AR表达和/或转移状态均等分组。随后运用多种生物信息学工具确定可能受影响的蛋白靶点及信号通路。研究发现，包括miR-328-3p和miR-489-3p在内的7种miRNA表达水平与AR表达呈显著正相关，而miR-205-3p的高表达与肿瘤转移显著相关。在转移性或非转移性AR阳性肿瘤中，特定miRNA呈现差异性表达。基因本体（GO）分析显示，这些miRNA在转录调控、细胞DNA损伤应答及转化生长因子-β（TGF-β）信号通路中具有生物学功能，同时在激酶及转录因子活性方面呈现富集特征。京都基因与基因组百科全书（KEGG）富集分析进一步验证了TGF-β通路及多种激酶依赖通路的参与。本研究揭示了AR在TNBC中的作用机制，并证实miRNA在介导AR对TNBC的影响中发挥关键作用。
MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer
肿瘤(癌症)患者之家