Effects of JAK2 and JAK2V617F MRNA targeting nanoparticule application on CGAS-sting pathway in myeloproliferative neoplasms

In this study, it was aimed to investigate the activity of cGAS-STING cytosolic DNA detection pathway in presence of JAK2V617F mutation which is one of the indicator mutations of myleproliferative neoplams. With this purpose, HEL and SET2 cell lines carrying JAK2V617F and K562 cell line possessing wild type JAK2, were stimulated with Nanoflare particles that form double stranded structures by matching JAK2 and JAK2V617F mRNAs. The expressions of genes related with cGAS-STING and JAK-STAT pathways were analised with real time PCR in cell lines which were incubated with Nanoflares for various time. The expressions of cGAS, STING, TBK1, IRF3, TLR9, JAK2, STAT1 ve STAT2 genes were investigated all three cell lines. Expression changes were observed for tested genes in HEL and SET2 as result of nanoparticle application. Limited expression changed was observed in K562 cell line. In short termed incubations variable expression values were observed with in half hour periods. In general, the expressions of cGAS-STING pathway genes were reached higher values for mutant nanoparticles than wild type ones. This result showed that the blockage of mutant JAK2 mRNA affected cGAS-STING pathway positively. This situation might be the result of suppresive effect of continuously active JAK2 on cGAS-STING pathway.