The pro-apoptosis and pro-inflammation role of LncRNA HIF1A-AS1 in Coxsackievirus B3-induced myocarditis via targeting miR-138

Background: Cardiomyocyte apoptosis and inflammation induced by Coxsackievirus B3 (CVB3) are key pathogenetic mechanisms in viral myocarditis. Alterations in microRNAs and lncRNAs are associated with cardiac remodeling. However, whether the microRNA and lncRNA interact to regulate cardiomyocyte apoptosis and inflammation is unknown. Methods: BALB/c mice were infected with CVB3 to generate acute viral myocarditis model. The expression levels of lncRNA HIF1A-AS1 and miR-138 were examined in mouse myocardium and primary cardiomyocytes with CVB3 infection. We then knocked down HIF1A-AS1 by siRNA and upregulated miR-138 by microRNA mimics in cardiomyocytes. Results: The expression of lncRNA HIF1A-AS1 was significantly increased in CVB3-induced myocardium and cardiomyocytes. As documented by flow cytometry, silencing of HIF1A-AS1 alleviated late apoptosis (5.1%+/- 12.8% vs. 17.2%+/- 4.2%, P<0.01) and ROS production (68.73%+/- 2.78% vs. 90.40%+/- 2.86%, P<0.01) compared to their levels in cardiomyocytes transfected with control siRNA. The content of proinflammatory cytokines was substantially decreased by HIF1A-AS1 siRNA. Furthermore, we identified that HIF1A-AS1 bound to miR-138 and significantly suppressed miR-138 expression. Blocking HIF1A-AS1 attenuated IxBa phosphorylation and NF-kappa B activity, while cotransfection with miR-138 mimics markedly reversed its effect. Conclusions: In conclusion, lncRNA HIF1A-AS1 promotes NF-kappa B signaling and subsequently aggravates cardiomyocyte apoptosis and inflammation via targeting miR-138.