NF-κB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2.

Angiotensin II(Ang II)-stimulated cardiomyocytes hypertrophy and apoptosis are associated with nuclear factor-κB (NF-κB) activation. NF-κB, a redox-sensitive transcription factor, contributes a critical role in cell death, but, Ang II-stimulated NF-κB-mediated cardiomyocytes apoptosis remains less understood. Recently, microRNAs (miRNAs) have been shown to be critical regulators in various cardiac remodeling processes; however, NF-κB-mediated miRNA's role in cardiomyocytes apoptosis remains undetermined. The miR-30b has been implicated in diverse cardiac remodeling; but, NF-κB-mediated miR-30b modulation in Ang II-induced cardiomyocytes death is currently unknown. In the present study, neonatal cardiomyocytes were pretreated with SN50, a selective cell permeable peptide inhibitor of NF-κB, or transfected with miR-30b mimetic and inhibitors separately, and then challenged with Ang II. The target gene, Bcl-2, and NF-κB transcriptional activity were analyzed. Our results demonstrated that NF-κB positively regulated miR-30b expression in Ang II-induced cardiomyocytes apoptosis, and Bcl-2 was a direct target for miR-30b. NF-κB further regulated the expression of Bcl-2 in the above setting. Furthermore, Ang II-induced cardiomyocytes apoptosis rescued by inhibiting either NF-κB or miR-30b provided an important role in cardiomyocytes cell death. We evaluated a critical role of NF-κB-mediated miR-30b modulation in Ang II-stimulated cardiomyocytes targeting Bcl-2. Our data may provide a new insight of miR-30b's role in myocardial infarction or ischemia.