Figure 7

Proposed model: importance of the miR-30 regulatory effects in cardiomyocytes following DOX exposure. Upon DOX treatment, there seems to be an acute increase of GATA-6 expression in cardiomyocytes. GATA-6 is able to repress miR-30 family expression, resulting in DOX-induced miR-30 downregulation. In turn, the expression levels of miR-30 targets are upregulated. Three of the miR-30 target genes are involved in the complex catecholamine/adrenergic pathway. A correct equilibrium of members is crucial in this signaling cascade, as AC-cAMP-PKA activation promotes cardiomyocyte contraction, whereas Gi impairs contraction but protects against apoptosis via Phosphoinositide 3-kinase/Protein kinase B. In addition, miR-30 represses BNIP3L, which is involved in mitochondrial death. miR-30 expression seems to be essential in regulating mitochondrial apoptotic pathways and it is able to partially counteract DOX-induced toxicity. Solid lines: previously described mechanisms, dashed lines: novel mechanisms