Cellular microRNA-214 contributes to H1N1 influenza A virus-mediated apoptosis through repression of anti-apoptotic factors Livin in A549 cells

Influenza A virus (IAV) infection results in host cell death and major tissue damage. MicroRNAs (miRNAs) play an important role in the regulation of gene expression and are involved in many cellular processes including inhibition of viral replication in infected cells. Recent studies have revealed that miR-214 is involved in a variety of biological processes, including apoptosis. However, the effects and mechanisms of miR-214 on influenza A virus mediated apoptosis have not been well understood. In this study, we found that several apoptosis-associated miRNAs were stimulated in influenza A virus-infected A549 cells by microRNA PCR array analysis and validated using qPCR in serum samples from patients with H1N1 infection. Because miR-214 was significantly upregulated among them, we investigated its function. We identified anti-apoptotic factors Livin as a direct target of miR-214 by bioinformatics analysis and confirmed by using luciferase activity assay and Western blot. Functional overexpression of miR-214 promoted A549 cells apoptosis induced by influenza A virus, while knockdown of miR-214 inhibited A549 cells apoptosis. Moreover, we demonstrated that silencing of Livin rescued the inhibition of cell apoptosis induced by miR-214 inhibitor in influenza A virus-infected A549 cells, whereas Livin overexpression could reverse the promotion of cell apoptosis induced by miR-214 mimic. Taken together, our findings indicate that miR-214 is involved in H1N1 influenza virus-mediated apoptosis through repression of anti-apoptotic factor Livin.