MicroRNA-501 promotes HBV replication by targeting HBXIP
MicroRNA-501 promotes HBV replication by targeting HBXIP
复制标题
MicroRNA-501 通过靶向 HBXIP 促进 HBV 复制。
DOI：
10.1016/j.bbrc.2012.12.071
复制
发表时间：
2013-01-25
影响因子：
3.1
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Jin, Jiang;Tang, Shanhong;Fan, Daiming
MicroRNAs(MiRNAs)可以负向调控基因表达，也可以诱导或抑制病毒复制。在本研究中，我们通过miRNA阵列分析发现，在稳定产生乙肝病毒的细胞系(HepG2.2.15)和其对照细胞系(HepG2)中，有10个miRNAs的表达存在差异。在高复制的HepG2细胞和组织中，MIR-501的表达显著上调。在保持高复制的肝细胞癌组织中，MIR-501的表达显著上调。下调miR-501可显著抑制HBVDNA复制，但不影响细胞生长。荧光素酶报告和免疫印迹分析表明，HBXIP是一种乙肝复制抑制因子，是miR-501的潜在靶点。此外，HBXIP的敲除挽救了在HepG2.2.15细胞中miR-501缺失后对乙肝病毒的抑制，表明miR-501部分通过靶向HBXIP诱导乙肝病毒复制。因此，miR-501基因的敲除可能为抑制乙肝病毒复制提供新的机制和治疗靶点。(C)2013 Elsevier Inc.保留所有权利。
MicroRNAs (miRNAs) can negatively regulate gene expression and also induce or inhibit viral replication. In the present study, we found 10 miRNAs were differentially expressed in a stable HBV-producing cell line (HepG2.2.15) compared with its control cell line (HepG2) by miRNA array analysis. miR-501 was significantly up-regulated in HepG2 cells and tissues with high-HBV replication. miR-501 expression was significantly up-regulated in hepatocellular carcinoma tissues, where HBV replication kept high. Down-regulating miR-501 could significantly inhibit HBV replication, but not influence the growth of HepG2.2.15 cells. Luciferase reporter and western blot assays revealed that HBXIP, an inhibitor of HBV replication, was a potential target of miR-501. Moreover, knockdown of HBXIP rescued the inhibition of HBV that occurred after the loss of miR-501 in HepG2.2.15 cells, suggesting that miR-501 induced HBV replication partially by targeting HBXIP. Thus, knockdown of miR-501 might provide a new mechanism and therapeutic target for inhibiting HBV replication. (C) 2013 Elsevier Inc. All rights reserved.