HBV suppresses ZHX2 expression to promote proliferation of HCC through miR-155 activation

International Journal of Cancer. Journal International Du Cancer
Xiaojia SongChunhong Ma

Abstract

Initiation of hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection is a complex process that includes both oncogene activation and tumor suppressor inhibition. The HBV X (HBx) protein has an important and complex role in processes leading to HCC. We previously identified the mammalian Zinc fingers and homeoboxes 2 (ZHX2) gene as an HCC-associated tumor suppressor gene. In the present study, we investigated whether the oncogenic properties of HBV and, more specifically, HBx, involved ZHX2 silencing. Our data indicates that ZHX2 expression is significantly decreased in tumor tissues from HBV-positive HCC patients and livers from HBV transgenic mice. In vitro and in vivo studies confirmed that HBV-encoded proteins, particularly HBx, inhibits both the expression and tumor suppression properties of ZHX2. Further analyses identified miR-155, a well-known oncomiR in various cancers, as an important link between HBx and ZHX2 inhibition. Increased miR-155 levels were found in HBV-positive tumors, livers of HBV transgenic mice and HBx-overexpressing hepatoma cell lines. MiR-155 overexpression reduced ZHX2 levels via miR-155 seed sites in the ZHX2 3'UTR, whereas blocking miR-155 levels led to increased ZHX2 levels. ...Continue Reading

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Citations

Feb 6, 2020·Viruses·Kristi L TurtonTrushar R Patel
Aug 10, 2020·The Journal of Pathology·Xiangguo YuChunhong Ma
May 28, 2019·International Journal of Cancer. Journal International Du Cancer·Yiyu ChenWeiyi Fang
Jul 20, 2019·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Erica L ClinkenbeardBrett T Spear
Sep 29, 2019·Molecular Aspects of Medicine·Diana GuleiIoana Berindan-Neagoe
May 30, 2021·Seminars in Cell & Developmental Biology·Meenakshi GuptaMaryam Sarwat

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