In silico analysis of CpG islands and miRNAs potentially regulating the JAK-STAT signalling pathway

Abstract

Introduction 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. Aim 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. Material and methods 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. Results 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). Conclusions 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.