Abstract
The present study aimed to investigate the regulatory effects of microRNA-138-5p (miR-138-5p) and sirtuin 1 (SIRT1) on the progression of heart failure (HF). The binding association between miR-138-5p and SIRT1 was assessed by the dual-luciferase reporter assay. By conducting reverse transcription-quantitative polymerase chain reaction and Western blotting, relative levels of SIRT1 and p53 regulated by miR-138-5p were detected. In vitro HF models were generated by hydrogen peroxide (H2O2) induction in AC-16 and human cardiomyocyte (HCM) cells, followed by detection of the regulatory effects of SIRT1 on cell apoptosis and p53 expression. MiR-138-5p was negatively correlated with the SIRT1 level in cardiomyocytes. By recognizing and specifically targeting SIRT1 3′-untranslated region (3′-UTR), miR-138-5p decreased the translational level of SIRT1 and inhibited its enzyme activity, thereby decreasing the deacetylation level of p53. Through downregulating SIRT1 and activating p53 signaling, miR-138-5p induced apoptosis in H2O2-induced AC-16 and HCM cells. By contrast, knockdown of miR-138-5p in the in vitro HF models significantly protected the cardiomyocytes. SIRT1 contributed toward alleviate HF by inhibiting cardiomyocyte apoptosis via enhancing the deacetylation level of p53. MiR-138-5p decreases the enzyme activity of SIRT1 by specifically targeting its 3′-UTR and activates p53 signaling, followed by triggering cardiomyocyte apoptosis during the process of HF. It is considered that miR-138-5p and SIRT1 may be potential diagnostic biomarkers and therapeutic targets for HF.
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