miR-224 suppresses HBV replication posttranscriptionally through inhibiting SIRT1-mediated autophagy

Hepatitis B virus (HBV) enters the host and successfully completes replication by using several mechanisms, including autophagy. However, previous studies revealed that microRNAs (miRNAs) widely participate in regulation of various cellular processes, such as autophagy and viral replication. Hence, the purpose of this study was to investigate the role of miR-224 in HBV infection and to determine whether its role depended on the miR-224/SIRT1/autophagy axis. Our results show that secretions of HBeAg and HBsAg, and HBV replication significantly declined in Huh7-1.3 cells, established by transfecting recombinant pcDNA 3.0-1.3 mer containing the 1.3 mer fragment of HBV genomic DNA,with miR-224 mimic transfection as compared to the Huh7-1.3 group. Moreover, it was discovered that HBV could induce autophagy, while miR-224 inhibited autophagy caused by HBV. Additionally, miR-224 could suppress SIRT1, LC3 expression, and facilitate p62 expression. SIRT1 was identified as the target gene of miR-224 and down-regulation of SIRT1 via miR-224 or si-SIRT1 transfected treatment in Huh7-1.3 cells repressed LC3 expression and enhanced p62 expression. In conclusion, these results suggest that miR-224 might hinder HBV replication through attenuating SIRT1-mediated autophagy, thereby these findings open a new avenue for the treatment of HBV infection.