Cytokines orchestrate responses to pathogens and in inflammatory processes, but they also play an important role in cancer by shaping the expression levels of cytokine response genes. Here, we conducted a large profiling study comparing miRNome and mRNA transcriptome data generated following different cytokine stimulations. Transcriptomic responses to STAT1- (IFNγ, IL-27) and STAT3-activating cytokines (IL6, OSM) were systematically compared in nine cancerous and non-neoplastic cell lines of different tissue origins (skin, liver and colon).

The largest variation in our datasets was seen between cell lines of the three different tissues rather than stimuli. Notably, the variability in miRNome datasets was a lot more pronounced than in mRNA data. Our data also revealed that cells of skin, liver and colon tissues respond very differently to cytokines and that the cell signaling networks activated or silenced in response to STAT1- or STAT3-activating cytokines are specific to the tissue and the type of cytokine. However, globally, STAT1-activating cytokines had stronger effects than STAT3-inducing cytokines with most significant responses in liver cells, showing more genes upregulated and with higher fold change. A more detailed analysis of gene regulations upon cytokine stimulation in these cells provided insights into STAT1- versus STAT3-driven processes in hepatocarcinogenesis. Finally, independent component analysis revealed interconnected transcriptional networks distinct between cancer cells and their healthy counterparts.

细胞因子协调了对病原体和炎症过程的反应，但它们也通过调节细胞因子反应基因的表达水平在癌症中发挥重要作用。在这里，我们进行了一项大型分析研究，比较了不同细胞因子刺激后产生的miRNome和mRNA转录组数据。在不同组织来源（皮肤，肝脏和结肠）的九种癌性和非肿瘤细胞系中，系统地比较了对STAT1-（IFNγ，IL-27）和STAT3激活细胞因子（IL6，OSM）的转录组反应。

我们的数据集中最大的差异是在三种不同组织的细胞系之间而不是在刺激之间。值得注意的是，miRNAome数据集中的变异性比mRNA数据明显得多。我们的数据还显示，皮肤，肝和结肠组织的细胞对细胞因子的反应非常不同，并且响应STAT1或STAT3激活的细胞因子而激活或沉默的细胞信号网络对组织和细胞因子的类型具有特异性。但是，在全球范围内，激活STAT1的细胞因子的作用要强于STAT3诱导的细胞因子，在肝细胞中的反应最为显着，显示出更多的上调基因和更高的倍数变化。对这些细胞中细胞因子刺激的基因调控的更详细分析提供了对STAT1与STAT3驱动的肝癌发生过程。最后，独立成分分析揭示了癌细胞与其健康对应物之间互不相同的相互连接的转录网络。