Influence of miR-520e-mediated MAPK signaling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2

Abstract This paper aims to determine the role of miR-520e in the replication of hepatitis B virus (HBV) and the growth of hepatocellular carcinoma (HCC) cells. MiR-520e and EphA2 in HBV-positive HCC tissues and cells were detected. HepG2.2.15 and Huh7 cells transfected with pHBV1.2 were divided into Mock, NC, miR-520e mimic, miR-520e inhibitor, si-EphA2, and miR-520e inhibitor + si-EphA2 groups. MiR-520e, HBV DNA content, HBsAg and HBeAg levels, cell proliferation, apoptosis and protein expression of EphA2 and MAPK pathways were evaluated. Furthermore, rAAV81.3HBV infected-mouse model was established to detect HBV-DNA levels. MiR-520e was up-regulated and EphA2 was down-regulated in HBV-positive HCC tissues and cells (HepG2.2.15 and HepAD38). MiR-520e was decreased in Huh7-X and HepG2-X cells in which HBx was stably expressed, but miR-520e was dose-dependently elevated in Huh7-X, HepG2-X, and HepG2.2.15 cells after interfering HBx. Additionally, miR-520e mimic and si-EphA2 groups were apparently reduced in HBV DNA content, HBsAg and HBeAg levels, cell proliferation, and were enhanced in the expressions of EphA2, MAPK pathways and cell apoptosis. Furthermore, si-EphA2 can reverse the promotion effect of miR-520e inhibitor on the HBV replication and tumor cell growth Up-regulating miR-520e in rAAV81.3HBV infected-mouse resulted in the reduced EphA2 in liver tissues and HBV DNA content in serum. MiR-520e was found to be decreased in HBV-positive HCC tissues and cells, while over-expression of miR-520e blocked MAPK pathways via inhibiting EphA2, ultimately reducing HBV replication and inhibiting tumor cell growth.