MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling

摘要: MicroRNAs (miRs) are a class of single-stranded, non-coding RNAs about 22 nucleotides in length. Increasing evidence implicates miRs myocardial disease processes. Here we show that miR-199b is direct calcineurin/NFAT target gene increases expression mouse and human heart failure, targets the nuclear NFAT kinase dual-specificity tyrosine-(Y)-phosphorylation regulated 1a (Dyrk1a), constituting pathogenic feed forward mechanism affects calcineurin-responsive expression. Mutant mice overexpressing miR-199b, or haploinsufficient for Dyrk1a, sensitized to signalling pressure overload stress-induced cardiomegaly through reduced Dyrk1a In vivo inhibition by specific antagomir normalized expression, activity caused marked even reversal hypertrophy fibrosis models failure. Our results reveal microRNAs affect cardiac cellular implicate as therapeutic