MicroRNA-21 protects cardiomyocytes from tumor necrosis factor-α induced apoptosis in vitro via modulating PTEN/AKT/FOXO3a pathway / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effect of microRNA-21 on tumor necrosis factor (TNF)-α induced cardiomyocytes apoptosis and the association with PTEN/AKT/FOXO3a signaling pathway.</p><p><b>METHODS</b>Neonatal cardiomyocytes were isolated and cultured in vitro. Cardiomyocytes apoptosis was induced by TNF-α (10 ng/ml for 24 h) and examined by the cardiomyocytes apoptotic index. Eukaryotic expression vector for lenti-microRNA-21 was established and then transferred into the cardiomyocytes. MicroRNA-21 and PTEN mRNA were examined by qRT-PCR. Intracellular signal molecules, such as the expression of PTEN, phosphorylated PTEN, AKT, phosphorylated AKT (pAKTser473, pAKTThr308), FOXO3a, phosphorylated FOXO3a and FasL were detected by Western blot.</p><p><b>RESULTS</b>MicroRNA-21 reduced TNF-α induced cardiomyocytes apoptosis [(23.42 ± 1.98)% vs. (78.37 ± 2.03)%, P < 0.05]. TNF-α downregulated the expression of microRNA-21 and upregulated the mRNA and protein expressions of PTEN. Phosphorylation of PTEN, AKT and FOXO3a was enhanced in cardiomyocytes transfected with lenti-microRNA-21 (P < 0.05). TNF-α also significantly activated the phosphorylation of PTEN, AKT and FOXO3a (P < 0.05). Compared with cardiomyocytes treated with TNF-α (10 ng/ml), the phosphorylation of PTEN, AKT and FOXO3a as well as expression of pPTEN, pAKTser473, pFOXO3a and FasL were significantly suppressed in cardiomyocytes treated with lenti-microRNA-21 and TNF-α (P < 0.05). Total AKT and FOXO3a were similar among all groups (P > 0.05).</p><p><b>CONCLUSIONS</b>MicroRNA-21 could protect cardiomyocytes from TNF-α- induced apoptosis through PTEN/AKT/FOXO3a pathway, which might serve as a new therapy option for various cardiovascular diseases in the future.</p>