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Influence of miR‐520e‐mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2
Author(s) -
Tian Jinghui,
Liu Wendong,
Zhang Zhiyong,
Tang Lihua,
Li Dong,
Tian Zhaoju,
Lin Shaowei,
Li Yingjie
Publication year - 2019
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.13048
Subject(s) - mapk/erk pathway , hepatitis b virus , eph receptor a2 , cell growth , hepatocellular carcinoma , cancer research , kinase , apoptosis , biology , viral replication , microbiology and biotechnology , chemistry , virology , virus , biochemistry , receptor tyrosine kinase
Summary 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 HB x was stably expressed, but was dose‐dependently elevated after interfering with HB x. Additionally, miR‐520e mimic and si‐EphA2 groups were reduced in association with increases in HBV DNA content, HB sAg and HB eAg levels, cell proliferation and were enhanced in the expressions of EphA2, p‐p38 MAPK /p38 MAPK , phosphorylated extracellular signal‐regulated kinase 1/2 (p‐ ERK 1/2)/ ERK 1/2 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 rAAV 8‐1.3 HBV ‐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 p38 MAPK and ERK 1/2 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.