Downregulation of lncRNA ZFAS1 protects H9c2 cardiomyocytes from ischemia/reperfusion-induced apoptosis via the miR-590-3p/NF-κB signaling pathway.

Long non-coding RNA (lncRNA) ZNFX1 antisense RNA 1 (ZFAS1) is upregulated in acute myocardial infarction; however, the role of ZFAS1 in myocardial ischemia/reperfusion (I/R) injury remains unknown. The present study aimed to detect microRNA (miR)-590-3p expression levels in cardiomyocytes subjected to I/R, and to investigate the effects of ZFAS1 on myocardial I/R injury. An in vitro model of I/R injury was established using rat H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R). It was demonstrated that ZFAS1 was upregulated and miR-590-3p was downregulated in the in vitro model of cardiac I/R injury. Western blotting results indicated that the protein expression levels of p50, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, Bax and cleaved caspase-3 were upregulated, and the expression levels of Bcl-2 and pro-caspase-3 were downregulated. Flow cytometry results revealed that downregulation of ZFAS1 reduced H/R-induced apoptosis in H9c2 cells. In addition, downregulation of ZFAS1 significantly increased the expression of miR-590-3p, and p50 was identified as a target gene of miR-590-3p. Furthermore, with 12 h of hypoxia followed by 2 h of reoxygenation in H9c2 cells, ZFAS1 knockdown increased the expression levels of miR-590-3p, Bax and cleaved-caspase-3, and decreased the expression levels of Bcl-2 and pro-caspase-3. It was also found that the miR-590-3p-mimic transfection increased the expression levels of Bax and cleaved-caspase-3, and decreased the protein expression levels of p50, TNF-α, IL-6, Bcl-2 and pro-caspase-3. In addition, TNF-α treatment induced apoptosis of H9c2 cells, and the changes in Bax, Bcl-2, cleaved-caspase-3 and pro-caspase-3 expression levels in a dose-dependent manner. Collectively, the present results suggested that ZFAS1 was upregulated in H9c2 cells subjected to I/R injury, and that ZFAS1 knockdown protected against I/R-induced myocardial cell apoptosis by directly interacting with miR-590-3p, via the NF-κB pathway. [ABSTRACT FROM AUTHOR]