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

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.

• Authors: Jingwen Wang, Jianwen Chen, Yang Liu, Xianhuang Zeng, Mingcong Wei, Shaoshuai Wu, Qiushuang Xiong, Feifei Song, Xu Yuan, Yu Xiao, Yun Cao, Changyong Li, Lang Chen, Mingxiong Guo, Yun-Bo Shi, Guihong Sun, Deyin Guo
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 69 Issue 3 Pg. 974-992 (03 2019) ISSN: 1527-3350 [Electronic] United States
• PMID: 30180281 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Chemical References

• Birc4 protein, mouse
• Inhibitor of Apoptosis Proteins
• MicroRNAs
• Mirn192 microRNA, mouse
• NF-kappa B

Topics

• Animals
• Autophagy (physiology)
• Cells, Cultured
• Hepatitis B virus (physiology)
• Inhibitor of Apoptosis Proteins (physiology)
• Mice
• MicroRNAs (physiology)
• NF-kappa B (physiology)
• Signal Transduction
• Virus Replication