Nicotinamide N-Methyltransferase inhibits HBV replication by suppressing NR5A1 expression in vitro

作者全名："Fan, Shu-ying; Long, Shao-yuan; Liu, Jia-jun; Zhang, Wen-lu; Hu, Jie-li"

作者地址："[Fan, Shu-ying; Long, Shao-yuan; Liu, Jia-jun; Zhang, Wen-lu; Hu, Jie-li] Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing, Peoples R China"

通信作者："Zhang, WL (通讯作者)，Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000804409100012

JCR分区：Q2

影响因子：3.1

年份：2022

卷号：614

期号：　

开始页：70

结束页：77

文献类型：Article

关键词：Hepatitis B virus; Nicotinamide N-Methyltransferase; Nuclear receptor subfamily 5 group A; member 1; Replication; Transcription

摘要："Chronic hepatitis B virus (HBV) infection can lead to fibrosis, liver cirrhosis, and primary hepatocellular carcinoma. Investigating host factors that regulate HBV replication helps to identify antiviral targets. In the current study, we identified Nicotinamide N-Methyltransferase gene (NNMT) as a novel factor that regulates HBV transcription. NNMT is up-regulated at both the mRNA and protein levels in HepG2.2.15 cells compared to HepG2 cells. Overexpression of NNMT reduces HBV replication in several cell models, while knockdown of NNMT enhances HBV DNA levels. Mechanistically, NNMT suppresses HBV DNA replication by inhibiting HBV RNA transcription. The region required for the inhibitory effect of NNMT was narrowed to nt 1672-1708 in enhancer II by luciferase assays. On the other hand, ChIP assays and EMSA results showed that NNMT does not bind to this region substantially, either directly or indirectly. Next, a collection of hepatic nuclear receptor transcription factors was screened to determine whether they were affected by NNMT overexpression. NR5A1, a positive regulator of HBV replication, decreased significantly after NNMT overexpression. Collectively, the findings of this study shed light on the regulation of HBV transcription. (c) 2022 Elsevier Inc. All rights reserved."

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