Systematic Transcriptional Profiling of Responses to STAT1- and STAT3-Activating Cytokines in Different Cancer Types. Issue 22 (6th November 2020)

• Record Type: Journal Article
• Authors: Kirchmeyer, Mélanie; Servais, Florence; Ginolhac, Aurélien; Nazarov, Petr V.; Margue, Christiane; Philippidou, Demetra; Nicot, Nathalie; Behrmann, Iris; Haan, Claude; Kreis, Stephanie
• Is Part Of: Journal of molecular biology. Volume 432:Issue 22(2020)
• Page Start: 5902
• Page End: 5919
• Publication Date: 2020-11-06
• Subjects: Transcriptome -- Signaling -- Cytokines -- Cancer -- Profiling; TCGA The Cancer Genome Atlas -- miRNA microRNA -- OSM Oncostatin M -- ICA independent component analysis -- PCA principal component analysis; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.09.011
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: 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. Graphical abstract: Unlabelled Image Highlights: Characterization of transcriptomic changes in cancer cells of three different tissues and following exposure to four distinct cytokines IFNγ-type/STAT1 responses mostly involved in anti-cancer signaling networks IL6-type/STAT3-activated gene profiles predominantly found in oncogenic signaling Liver cells had stronger responses to cytokines than skin and colon cells Detailed investigation of gene regulation responses following cytokine-triggered activation of either STAT1 or STAT3 transcription factors