Synergistic effects of the GATA-4-mediated miR-144/451 cluster in protection against simulated ischemia/reperfusion-induced cardiomyocyte death

►The miR-144/451 cluster is directly regulated by cardiac transcription factor GATA-4. ►Increased levels of miR-144 and miR-451 protect adult cardiomyocytes against simulated ischemia/reperfusion-induced cell death, and overexpression of miR-144/451 reveals additive effects on cardioprotection. ►Both miR-144 and miR-451 target CUGBP2, an RNA-binding protein, which interacts with COX-2 3′UTR and inhibits its mRNA translation. ►COX-2 is upregulated in miR-144-, miR-451-, and miR-144/451-overexpressing cardiomyocytes. ►Inhibition of COX-2 partially abrogates miR-144/451-mediated cardioprotection.