LAUSR

We determined the role of miR‐520e in the replication of hepatitis B virus (HBV) and the growth of hepatocellular carcinoma (HCC) cells. MiR‐520e and EPH receptor A2 (EphA2) in HBV‐positive HCC tissues and cells were detected, and we studied the impact of miR‐520e and the EphA2 receptor in cellular and murine HBV replication models. We find that MiR‐520e was upregulated and EphA2 was downregulated in HBV‐positive HCC tissues and cells. MiR‐520e was decreased in Huh7‐X and HepG2‐X cells in which HBx was stably expressed, but was dose‐dependently elevated after interfering with HBx. Additionally, miR‐520e mimic and si‐EphA2 groups were reduced in association with increases in HBV DNA content, HBsAg and HBeAg levels, cell proliferation and were enhanced in the expressions of EphA2, p‐p38MAPK/p38MAPK, phosphorylated extracellular signal‐regulated kinase 1/2 (p‐ERK1/2)/ERK1/2 and cell apoptosis. Furthermore, si‐EphA2 reversed the promotion effect of miR‐520e inhibitor on HBV replication and tumour cell growth. Upregulating miR‐520e in rAAV8‐1.3HBV‐infected mouse resulted in reduced EphA2 in liver tissues and HBV DNA content in serum. We find that MiR‐520e was decreased in HBV‐positive HCC, while overexpression of miR‐520e blocked p38MAPK and ERK1/2 signalling pathways by an inhibitory effect on EphA2 and ultimately reduced HBV replication and inhibited tumour cell growth. These data indicate a role for miR‐520e in the regulation of HBV replication.