Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. A-to-I editing of RNA is a widespread posttranscriptional process that has recently emerged as an important mechanism in cancer biology[2]. 8-Azaadenosine is a potent ADAR1 inhibitor and an A-to-I editing inhibitor. 8-Azaadenosine blocks RNA editing and inhibits proliferation, 3D growth, invasion, and migration in thyroid cancer cells. 8-Azaadenosine targets ADAR (adenosine deaminases acting on double-stranded RNA) activity only and does not affect ADAR1 mRNA levels. 8-Azaadenosine (10-25 nM) restores let-7 miRNA biogenesis commensurate with a reduction in ADAR1 expression, RNA editing activity and LIN28B expression in JAK2/BCR-ABL1 transduced progenitors after two weeks in stromal co-culture. 8-Azaadenosine (10, 100 nM) shows no effect on BCR-ABL and JAK2 signaling[1]. 8-Azaadenosine (0.1, 0.5, 1, 2 µM; 5 days) decreases cell viability/proliferation in a dose-dependent manner in TPC1 and Cal62 cells. 8-Azaadenosine (1, 2 µM) impedes invasion and migration and inhibits the editing activity of TPC1 and Cal62 cells. By contrast, ADAR1 mRNA levels remains stable in both cells lines[2]. In H. Ep. 2 cells, 8-aza-HR blocked the conversion of orotic acid to uridine nucleotides and caused an accumulation of orotidine. This inhibition of pyrimidine biosynthesis apparently does not contribute significantly to the cytotoxicity of 8-aza-HR because uridine provided no degree of reversal of its inhibition of the growth of cell cultures[3].
搜索
