Lukowski Samuel W, Fish Richard J, Martin-Levilain Juliette, Gonelle-Gispert Carmen, Bühler Leo H, Maechler Pierre, Dermitzakis Emmanouil T, Neerman-Arbez Marguerite
Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland.
Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland.
Genomics. 2015 Aug;106(2):107-15. doi: 10.1016/j.ygeno.2015.05.001. Epub 2015 May 12.
The expression of plasma proteins changes dramatically as a result of cytokine induction, particularly interleukin-6, and their levels are used as clinical markers of inflammation. miRNAs are important regulators of gene expression and play significant roles in many inflammatory diseases and processes. The interactions between miRNAs and the genes that they regulate during the acute phase response have not been investigated. We examined the effects of IL-6 stimulation on the transcriptome and miRNome of human and mouse primary hepatocytes and the HepG2 cell line. Using an integrated analysis, we identified differentially expressed miRNAs whose seed sequences are significantly enriched in the 3' untranslated regions of differentially expressed genes, many of which are involved in inflammation-related pathways. Our finding that certain miRNAs may de-repress critical acute phase proteins within acute timeframes has important biological and clinical implications.
由于细胞因子诱导，特别是白细胞介素-6，血浆蛋白的表达发生显著变化，其水平被用作炎症的临床标志物。微小RNA（miRNA）是基因表达的重要调节因子，在许多炎症性疾病和过程中发挥重要作用。在急性期反应期间，miRNA与其调控基因之间的相互作用尚未得到研究。我们研究了白细胞介素-6刺激对人和小鼠原代肝细胞以及HepG2细胞系转录组和miRNA组的影响。通过综合分析，我们鉴定出差异表达的miRNA，其种子序列在差异表达基因的3'非翻译区显著富集，其中许多基因参与炎症相关途径。我们的发现表明，某些miRNA可能在急性时间范围内解除对关键急性期蛋白的抑制，这具有重要的生物学和临床意义。
