title: NF-κB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2.
abstract: 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.
authors.affiliation: Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A & M Health Science Center, Temple, TX, USA.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Sudhiranjan
authors.initials: S
authors.lastname: Gupta
mesh_terms: D020413:3' Untranslated Regions; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D020413:3' Untranslated Regions; C556157:MIRN30 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D000804:Angiotensin II