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Hepatitis B Virus Induces Autophagy to Promote its Replication by the Axis of miR‐192‐3p‐XIAP Through NF kappa B Signaling
Author(s) -
Wang Jingwen,
Chen Jianwen,
Liu Yang,
Zeng Xianhuang,
Wei Mingcong,
Wu Shaoshuai,
Xiong Qiushuang,
Song Feifei,
Yuan Xu,
Xiao Yu,
Cao Yun,
Li Changyong,
Chen Lang,
Guo Mingxiong,
Shi YunBo,
Sun Guihong,
Guo Deyin
Publication year - 2019
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30248
Subject(s) - xiap , hepatitis b virus , microrna , viral replication , virology , cancer research , autophagy , biology , hepatocellular carcinoma , virus , apoptosis , gene , programmed cell death , caspase , genetics
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.