miRNA-548ah通过靶向组蛋白去乙酰化酶4促进乙型肝炎病毒的复

StephenW

Life Sci. 2019 Jan 4. pii: S0024-3205(18)30858-0. doi: 10.1016/j.lfs.2018.12.057. [Epub ahead of print]
miRNA-548ah promotes the replication and expression of hepatitis B virus by targeting histone deacetylase 4.
Xing T1, Zhu J2, Xian J3, Li A2, Wang X2, Wang W3, Zhang Q3.
Author information

1
    Department of Infectious Diseases, Taizhou Hospital of Wenzhou Medical University, Linhai, Zhejiang Province, China. Electronic address: [email protected].
2
    Department of Infectious Diseases, Taizhou Hospital of Wenzhou Medical University, Linhai, Zhejiang Province, China.
3
    Department of Infectious Diseases, Taizhou People's Hospital, Taizhou, Jiangsu Province, China.

Abstract
AIM:

Many studies have shown that some microRNAs (miRNAs) play an important role in the pathogenesis of chronic hepatitis B (CHB) infection. In this study, we aimed to explore the role and molecular mechanism of miRNA-548ah in the replication and expression of the hepatitis B virus (HBV).
MAIN METHODS:

Overexpression and knockdown of miRNA-548ah were performed in three hepatoma cell lines with HBV replication and in a murine HBV model injected with adenovirus HBV vector. The effect of miRNA-548ah on its target gene, histone deacetylase (HDAC) 4, were confirmed in in vitro studies and further investigated in liver tissues from CHB patients.
KEY FINDINGS:

miRNA-548ah significantly increased the expression of HBV in hepatoma cell lines and in a HBV mouse model. The expression level of covalently closed circular DNA (cccDNA) in the miRNA-548ah mimics group was significantly higher than the negative control group and significantly lower in the miRNA-548ah inhibitor group. The HBV core antigen promotes the expression of miRNA-548ah in hepatocytes. Finally, we observed a negative correlation between the expression of miRNA-548ah and HDAC4 in the liver tissue of patients with CHB.
SIGNIFICANCE:

miRNA-548ah promoted the replication and expression of HBV through the regulation of the target gene, HDAC4. Inhibition of HDAC4 by miRNA-548ah might influence the deacetylation state of histones binding to cccDNA, thereby enhancing the replication of cccDNA. The HBV core antigen might increase the expression of miRNA-548ah. These results may provide new potential molecular targets for the prevention and treatment of CHB.

Copyright © 2019. Published by Elsevier Inc.
KEYWORDS:

Chronic hepatitis B; Deacetylation; Histone deacetylase 4; microRNA-548ah

PMID:
    30615846
DOI:
    10.1016/j.lfs.2018.12.057

StephenW

生命科学。 2019年1月4日.pii：S0024-3205（18）30858-0。 doi：10.1016 / j.lfs.2018.12.057。 [提前打印]
miRNA-548ah通过靶向组蛋白去乙酰化酶4促进乙型肝炎病毒的复制和表达。
邢T1，朱J2，西安J3，李A2，王X2，王W3，张Q3。
作者信息

1
    温州医科大学附属台州医院感染科，浙江省临海市电子地址：[email protected]。
2
    温州医科大学附属台州医院感染科，浙江省临海市
3
    中国江苏省泰州市台州市人民医院感染科

抽象
目标：

许多研究表明，一些microRNA（miRNA）在慢性乙型肝炎（CHB）感染的发病机制中起重要作用。在本研究中，我们旨在探讨miRNA-548ah在乙型肝炎病毒（HBV）复制和表达中的作用和分子机制。
主要方法：

在具有HBV复制的三个肝细胞瘤细胞系和注射腺病毒HBV载体的鼠HBV模型中进行miRNA-548ah的过表达和敲低。 miRNA-548ah对其靶基因组蛋白去乙酰化酶（HDAC）4的作用在体外研究中得到证实，并在CHB患者的肝组织中进一步研究。
主要发现：

miRNA-548ah显着增加了HBV在肝癌细胞系和HBV小鼠模型中的表达。 miRNA-548ah模拟组中共价闭合环状DNA（cccDNA）的表达水平显着高于阴性对照组，并且在miRNA-548ah抑制剂组中显着降低。 HBV核心抗原促进肝细胞中miRNA-548ah的表达。最后，我们观察到CHB患者肝组织中miRNA-548ah和HDAC4的表达呈负相关。
意义：

miRNA-548ah通过调节靶基因HDAC4促进HBV的复制和表达。 miRNA-548ah对HDAC4的抑制可能影响组蛋白与cccDNA结合的脱乙酰化状态，从而增强cccDNA的复制。 HBV核心抗原可能增加miRNA-548ah的表达。这些结果可能为预防和治疗CHB提供新的潜在分子靶点。

版权所有©2019。Elsevier Inc.出版
关键词：

慢性乙型肝炎;脱乙酰度;组蛋白去乙酰化酶4;微小RNA-548ah

结论：
    30615846
DOI：
    10.1016 / j.lfs.2018.12.057