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Hepatology. 2019 Mar;69(3):974-992. doi: 10.1002/hep.30248.

Hepatitis B Virus Induces Autophagy to Promote its Replication by the Axis of miR-192-3p-XIAP Through NF kappa B Signaling.

Author information

1
School of Basic Medical Sciences, Wuhan University, Wuhan, China.
2
Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
3
Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD.
4
Hubei Provincial Key Laboratory of Allergy and Immunology, Wuhan, China.
5
Laboratory of Medical Virology, School of Medicine, Sun Yat-sen University, Guangzhou, China.

Abstract

Hepatitis B virus (HBV) is a major risk factor for the development and progression of hepatocellular carcinoma. It has been reported that viral infection can interfere with cellular microRNA (miRNA) expression and participate in the pathogenesis of oncogenicity. Here, we report that decreasing levels of the expression of the miRNA miR-192-3p is associated with rising levels of HBV DNA in the serum of HBV patients. We revealed that HBV infection repressed the expression of miR-192-3p through hepatitis B x protein interaction with c-myc. We further showed that miR-192-3p was repressed by HBV transfection in vitro and in a mouse model, leading to cellular autophagy. Using an miRNA target prediction database miRBase, we identified X-linked inhibitor of apoptosis protein (XIAP) as a target gene of miR-192-3p and demonstrated that miR-192-3p directly targeted the XIAP 3'-untranslated region of XIAP messenger RNA. Importantly, we discovered that HBV promoted autophagy through miR-192-3p-XIAP axis and that this process was important for HBV replication in vitro and in vivo. We demonstrated that miR-192-3p functioned through the nuclear factor kappa B signaling pathway to inhibit autophagy, thereby reducing HBV replication. Conclusions: Our findings indicate that miR-192-3p is a regulator of HBV infection and may play a potential role in hepatocellular carcinoma. It may also serve as a biomarker or therapeutic target for HBV patients.

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