Upregulation of miR-144-3p protects myocardial function from ischemia –reperfusion injury through inhibition of TMEM16A Ca 2+ -activated chloride channel
In this study, we investigated the underlying molecular mechanism of miR-144-3p in the pathological process of MIRI. A mouse I/R injury model and H9c2 cardiomyocyte hypoxia/reoxygenation (H/R) model were used to simulate the ischemia/reperfusion process in vivo and in vitro, respectively, and the relative expression and regulatory effect of miR-144-3p were determined. The target of miR-144-3p was also verified by a luciferase reporter assay. We found that miR-144-3p was significantly downregulated in mouse myocardium subjected to I/R and cardiomyocytes subjected to H/R. Upregulation of miR-144-3p significantly attenuated MIRI in vivo and in vitro. A Ca2+-activated chloride channel —TMEM16A (ANO1)—was identified as a target gene of miR-144-3p through bioinformatic analysis. The interaction between miR-144-3p and the 3ʹ-untranslated region of ANO1 was confirmed with dual-luciferase reporter assay, RNA immunoprecipitation assay, real-time quantitative polymerase chain react ion, and western blot analysis. Moreover, by targeting ANO1, miR-144-3p inhibited the activation of NLRP3 inflammasome inflammatory signals in myocardial cells. Collectively, the present study provides a novel insight into the role of miR-144-3p in the inhibition of MIRI, suggesting that the miR-144 -3p/ANO1 axis may be a putative therapeutic target in myocardial ischemia.
Source: Human Cell - Category: Cytology Source Type: research