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  • Title: MicroRNA-148b-3p is involved in regulating hypoxia/reoxygenation-induced injury of cardiomyocytes in vitro through modulating SIRT7/p53 signaling.
    Author: Sun M, Zhai M, Zhang N, Wang R, Liang H, Han Q, Jia Y, Jiao L.
    Journal: Chem Biol Interact; 2018 Dec 25; 296():211-219. PubMed ID: 30308185.
    Abstract:
    Accumulating evidence has suggested that microRNAs (miRNAs) are emerging as critical regulators in myocardial ischemia/reperfusion injury. miR-148b-3p has been reported to regulate cell apoptosis of various cell types. However, whether miR-148b-3p is involved in regulating cardiomyocyte apoptosis in myocardial ischemia/reperfusion injury remains unknown. In this study, we aimed to investigate the potential role and molecular mechanism of miR-148b-3p in regulating cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury in vitro, a cellular model of myocardial ischemia/reperfusion injury. We found that miR-148b-3p expression was significantly up-regulated in response to H/R treatment in cardiomyocytes. Functional experiments showed that miR-148b-3p overexpression significantly decreased the viability, increased LDH release and promoted the apoptosis of H/R-treated cardiomyocytes. In contrast, miR-148b-3p inhibition improved the viability, decreased LDH release and reduced the apoptosis of H/R-treated cardiomyocytes, showing a protective effect against H/R-induced injury. Bioinformatics analysis predicted that Sirtuin7 (SIRT7), a critical stress survival gene of cardiomyocytes, was a potential target gene of miR-148b-3p, which was then validated by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction and Western blot analysis. Moreover, our results showed that miR-148b-3p regulated the acetylation of the p53 protein and modulated p53-mediated pro-apoptotic signaling through targeting SIRT7. Notably, the silencing of SIRT7 significantly abrogated miR-148b-3p inhibition-mediated cardio-protective effects, while SIRT7 overexpression rescued miR-148b-3p-induced cell apoptosis in cardiomyocytes with H/R treatment. Overall, our results indicate that miR-148b-3p contributes to the regulation of H/R-induced cardiomyocyte apoptosis in vitro through targeting SIRT7 and modulating p53-mediated pro-apoptotic signaling.
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