RESUMEN
MicroRNAs (miRs) regulate a number of physiological and pathological processes, including myocardial chronic hypoxia. Previous studies revealed that the expression of miR-146b is increased in vitro and in vivo following the induction of hypoxia. In the present study, the role of miR146b in hypoxic cardiomyocytes, and the mechanisms underlying its activity, were investigated. The expression of miR146b was measured in tissue samples from patients with congenital heart disease by reverse transcriptionquantitative polymerase chain reaction. The rat H9c2 cardiomyocyte cell line was transfected with an miR146b inhibitor or the experimental controls, and the cells were maintained under hypoxic conditions for 72 h. The expression of miR146b increased following the induction of hypoxia. Transfection with the miR146b inhibitor enhanced the release of lactate dehydrogenase and increased hypoxiainduced apoptosis, as determined by terminal deoxynucleotidyl transferase dUTP nickend labeling, Hoechst 33258 staining, JC1 assay (measuring mitochondrial membrane permeability) and annexin V/propidium iodide analysis. A decreased expression of Bcl2 was observed, whereas the expression levels of cleavedcaspase 3 and Bax were increased. Western blot analysis and a dual luciferase reporter assay confirmed that ribonuclease L is a direct target of miR146b. Furthermore, inhibition of miR-146b increased the activation of nuclear factor-κB and signal transducer and activator of transcription 3. In conclusion, the inhibition of miR146b may increase hypoxia-induced cardiomyocyte apoptosis.