Grabarek Beniamin O, Wcisło-Dziadecka Dominika, Gola Joanna
Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland.
Department of Histology, Cytophysiology and Embryology in Zabrze, University of Technology in Katowice, Faculty of Medicine in Zabrze, Poland.
Postepy Dermatol Alergol. 2020 Aug;37(4):513-519. doi: 10.5114/ada.2020.98245. Epub 2020 Sep 2.
Searching for new therapeutic possibilities constitutes a challenge for modern medicine and an answer to better understanding of molecular mechanisms of pro-inflammatory diseases. The JAK-STAT pathway plays an important role in the inflammatory processes, which is supported by the fact that its inhibitors are used to treat, for instance, psoriasis and rheumatoid arthritis.
To determine whether the epigenetic mechanisms - methylation of gene promotion regions and miRNAs may serve as a new therapeutic strategy for JAK-STAT pathway inhibition.
Basing on MethPrimer (plus CpG Island Prediction) program and microrna.org database of the said mechanism in the regulation of the JAK-STAT signalling pathway, the gene expression was performed, indicating or excluding the possibility of their use as new potential therapeutic strategies.
A different number of CpG islands (CGI) for each gene (JAK1-4 CGI; JAK2-2 CGI; JAK3-5 CGI, TYK2-6 CGI; STAT1-2 CGI; STAT2-1 CGI; STAT3-3 CGI; STAT5A-4 CGI; STAT5B-3 CGI) might be a new therapeutic goal. What is more, our results show that genes associated with JAK-STAT signalling pathways can be regulated by miRNAs (JAK1-42 miRNAs; JAK2-47 miRNAs; JAK3-15 miRNAs, TYK2-4 miRNAs; STAT1-17 miRNAs; STAT2-30 miRNAs, STAT3-36 miRNAs, STAT4-15 miRNAs; STAT5A-10 miRNAs; STAT5B-23 miRNAs).
The epigenetic mechanisms of the regulation of the JAK-STAT signalling pathway gene expression constitute a promising new therapeutic strategy for treatment of those diseases, during which disorders are observed in gene expression models of the analysed signalling pathway.
寻找新的治疗方法是现代医学面临的一项挑战，也是更好地理解促炎性疾病分子机制的关键。JAK-STAT信号通路在炎症过程中发挥着重要作用，这一点从其抑制剂被用于治疗例如银屑病和类风湿性关节炎等疾病得到了证实。
确定表观遗传机制——基因启动子区域甲基化和微小RNA（miRNA）是否可作为抑制JAK-STAT信号通路的新治疗策略。
基于MethPrimer（加CpG岛预测）程序以及上述机制在JAK-STAT信号通路调控中的microrna.org数据库，进行基因表达分析，以表明或排除其作为新的潜在治疗策略的可能性。
每个基因（JAK1 - 4个CpG岛；JAK2 - 2个CpG岛；JAK3 - 5个CpG岛，TYK2 - 6个CpG岛；STAT1 - 2个CpG岛；STAT2 - 1个CpG岛；STAT3 - 3个CpG岛；STAT5A - 4个CpG岛；STAT5B - 3个CpG岛）的CpG岛数量不同，这可能成为一个新的治疗靶点。此外，我们的结果表明，与JAK-STAT信号通路相关的基因可受miRNA调控（JAK1 - 42种miRNA；JAK2 - 47种miRNA；JAK3 - 15种miRNA，TYK2 - 4种miRNA；STAT1 - 17种miRNA；STAT2 - 30种miRNA，STAT3 - 36种miRNA，STAT4 - 15种miRNA；STAT5A - 10种miRNA；STAT5B - 23种miRNA）。
JAK-STAT信号通路基因表达调控的表观遗传机制构成了一种有前景的新治疗策略，可用于治疗那些在分析的信号通路基因表达模型中出现紊乱的疾病。
