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Integrated MicroRNA-mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer

机译:整合microRNa-mRNa分析鉴定制瘤素m作为间充质样ER阴性/ HER2阴性乳腺癌的标志物

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摘要

MicroRNAs (miRNAs) simultaneously modulate different oncogenic networks, establishing a dynamic system of gene expression and pathway regulation. In this study, we analyzed global miRNA and messenger RNA (mRNA) expression profiles of 17 cell lines representing different molecular breast cancer subtypes. Spearman's rank correlation test was used to evaluate the correlation between miRNA and mRNA expression. Hierarchical clustering and pathway analysis were also performed. Publicly available gene expression profiles (n = 699) and tumor tissues (n = 80) were analyzed to assess the relevance of key miRNA-regulated pathways in human breast cancer. We identified 39 significantly deregulated miRNAs, and the integration between miRNA and mRNA data revealed the importance of immune-related pathways, particularly the Oncostatin M (OSM) signaling, associated with mesenchymal-like breast cancer cells. OSM levels correlated with genes involved in the inflammatory response, epithelial-to-mesenchymal transition (EMT), and epidermal growth factor (EGF) signaling in human estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Our results suggest that the deregulation of specific miRNAs may cooperatively impair immune and EMT pathways. The identification of the OSM inflammatory pathway as an important mediator of EMT in triple-negative breast cancer (TNBC) may provide a novel potential opportunity to improve therapeutic strategies.
机译:MicroRNA(miRNA)同时调节不同的致癌网络,建立了基因表达和途径调控的动态系统。在这项研究中,我们分析了代表不同分子乳腺癌亚型的17种细胞系的总体miRNA和信使RNA(mRNA)表达谱。使用Spearman秩相关检验评估miRNA与mRNA表达之间的相关性。还进行了层次聚类和路径分析。分析了公众可获得的基因表达谱(n = 699)和肿瘤组织(n = 80),以评估人类乳腺癌中关键的miRNA调控途径的相关性。我们确定了39个显着失调的miRNA,并且miRNA和mRNA数据之间的整合揭示了免疫相关途径的重要性,尤其是与间充质样乳腺癌细胞相关的Oncostatin M(OSM)信号传导。 OSM水平与人类雌激素受体(ER)阴性/人类表皮生长因子受体2(HER2)阴性的炎症反应,上皮间质转化(EMT)和表皮生长因子(EGF)信号传导相关的基因相关乳腺癌。我们的结果表明,特定miRNA的失控可能会协同损害免疫和EMT途径。 OSM炎症途径作为三阴性乳腺癌(TNBC)中EMT的重要介体的鉴定,可能为改善治疗策略提供新的潜在机会。

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