MicroRNAs (miRNAs) can negatively regulate gene expression and also induce or inhibit viral replication. In the present study, we found 10 miRNAs were differentially expressed in a stable HBV-producing cell line (HepG2.2.15) compared with its control cell line (HepG2) by miRNA array analysis. miR-501 was significantly up-regulated in HepG2 cells and tissues with high-HBV replication. miR-501 expression was significantly up-regulated in hepatocellular carcinoma tissues, where HBV replication kept high. Down-regulating miR-501 could significantly inhibit HBV replication, but not influence the growth of HepG2.2.15 cells. Luciferase reporter and western blot assays revealed that HBXIP, an inhibitor of HBV replication, was a potential target of miR-501. Moreover, knockdown of HBXIP rescued the inhibition of HBV that occurred after the loss of miR-501 in HepG2.2.15 cells, suggesting that miR-501 induced HBV replication partially by targeting HBXIP. Thus, knockdown of miR-501 might provide a new mechanism and therapeutic target for inhibiting HBV replication.
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