乙型肝炎病毒通过NF-κB信号通过miR-192-3p-XIAP的轴诱导自噬以

StephenW

Hepatology. 2018 Sep 4. doi: 10.1002/hep.30248. [Epub ahead of print]
Hepatitis B Virus Induces Autophagy to Promote its Replication by the Axis of miR-192-3p-XIAP via NF-κB Signaling.
Wang J1, Chen J1, Liu Y1, Zeng X1, Wei M1, Wu S1, Xiong Q1, Song F1, Yuan X1, Xiao Y1, Cao Y1, Li C1, Chen L1, Guo M2, Shi YB3, Sun G1,4, Guo D5.
Author information

1
    School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. China.
2
    Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.
3
    Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr, Bethesda, Maryland, 20892.
4
    Hubei Provincial Key Laboratory of Allergy and Immunology, Wuhan, P.R. China.
5
    Laboratory of Medical Virology, School of Medicine, Sun Yat-sen University, Guangzhou, 510080, P.R. China.

Abstract

Hepatitis B virus (HBV) is a major risk factor for the development and progression of hepatocellular carcinoma (HCC). 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 HBx interaction with c-Myc. We further showed that miR-192-3p was repressed by HBV transfection in vitro and in mouse model, leading to cellular autophagy. Using an miRNA target prediction database miRBase, we identified XIAP as a novel target gene of miR-192-3p and demonstrated that miR-192-3p directly targeted XIAP 3'-untranslated region (3'-UTR) of XIAP mRNA. 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 NF-κB signaling pathway to inhibit autophagy, thereby reducing HBV replication. Our findings indicate that miR-192-3p is a novel regulator of HBV infection and may play a potential role in HCC. It may also serve as a new biomarker or therapeutic target for HBV patients. This article is protected by copyright. All rights reserved.
KEYWORDS:

HBV ; XIAP ; NF-κB; autophagy; miR-192-3p

PMID:
    30180281
DOI:
    10.1002/hep.30248

StephenW

肝病。 2018年9月4日：doi：10.1002 / hep.30248。 [提前打印]
乙型肝炎病毒通过NF-κB信号通过miR-192-3p-XIAP的轴诱导自噬以促进其复制。
王J1，陈J1，刘Y1，曾X1，魏M1，吴S1，熊Q1，宋F1，袁X1，肖Y1，曹Y1，李C1，陈L1，郭M2，施YB3，太阳G1,4，郭D5。
作者信息

1
    武汉大学基础医学院，武汉430071，中国。
2
    武汉大学生命科学学院，湖北省细胞稳态重点实验室，武汉430072，中国。
3
    分子形态发生部分，Eunice Kennedy Shriver国立儿童健康与人类发展研究所（NICHD），国立卫生研究院（NIH），18 Library Dr，Bethesda，Maryland，20892。
4
    湖北省过敏与免疫重点实验室，武汉，中国。
五
    中山大学医学院医学病毒学实验室，广州，510080，中国。

抽象

乙型肝炎病毒（HBV）是肝细胞癌（HCC）发展和进展的主要危险因素。据报道，病毒感染可以干扰细胞microRNA（miRNA）的表达并参与致癌性的发病机制。在这里，我们报告miRNA miR-192-3p表达水平的降低与HBV患者血清中HBV DNA水平升高有关。我们发现HBV感染通过HBx与c-Myc的相互作用抑制miR-192-3p的表达。我们进一步显示miR-192-3p在体外和小鼠模型中被HBV转染抑制，导致细胞自噬。使用miRNA靶预测数据库miRBase，我们将XIAP鉴定为miR-192-3p的新靶基因，并证明miR-192-3p直接靶向XIAP mRNA的XIAP 3'-非翻译区（3'-UTR）。重要的是，我们发现HBV通过miR-192-3p-XIAP轴促进自噬，并且该过程对于体外和体内HBV复制是重要的。我们证明了miR-192-3p通过NF-κB信号通路起作用以抑制自噬，从而减少HBV复制。我们的研究结果表明，miR-192-3p是一种新的HBV感染调节因子，可能在HCC中发挥潜在作用。它还可以作为HBV患者的新生物标志物或治疗靶标。本文受版权保护。版权所有。
关键词：

HBV; XIAP; NF-κB;自噬;的miR-192-3p

结论：
    30180281
DOI：
    10.1002 / hep.30248