MicroRNA – 1可调节HBV复制及肝细胞分化

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作者： Pei R,Ma Z,Lu M,et al. 出处：

Hepatology (Baltimore, Md.).2011-05;53(5):1476-85.

文献类型：

其他 PMID: 21520166

Abstract：

MicroRNAs (miRNAs) are highly conserved small noncoding RNAs participating in regulation o... MicroRNAs (miRNAs) are highly conserved small noncoding RNAs participating in regulation of various cellular processes. Viruses have been shown to utilize cellular miRNAs to increase their replication in host cells. Until now, the role of miRNAs in hepatitis B virus (HBV) replication has remained largely unknown. In this study, a number of miRNA mimics were transfected into hepatoma cell lines with HBV replication. It was noted that microRNA-1 (miR-1) transfection resulted in a marked increase of HBV replication, accompanied with up-regulated HBV transcription, antigen expression, and progeny secretion. However, bioinformatics and luciferase reporter analysis suggested that miR-1 may not target the HBV genome directly but regulate the expression of host genes to enhance HBV replication. Further studies showed that miR-1 was able to enhance the HBV core promoter transcription activity by augmenting farnesoid X receptor α expression. In addition, miR-1 arrested the cell cycle at the G(1) phase and inhibited cell proliferation by targeting histone deacetylase 4 and E2F transcription factor 5. Analysis of the cellular gene expression profile indicated that miR-1 transfected hepatoma cells developed a differentiated phenotype of hepatocytes. CONCLUSION: MiR-1 regulates the expression of several host genes to enhance HBV replication and reverse cancer cell phenotype, which is apparently beneficial for HBV replication. Our findings provide a novel perspective on the role of miRNAs in host-virus interactions in HBV infection.

中文摘要：

MicroRNAs（miRNAs）是一种高度保守的非编码小RNAs，其参与各种细胞过程的调节。我们已证明了病毒可利用细胞中的miRNAs增加其在宿主细胞内的复制。至今，我们对miRNAs在乙型肝炎病毒（HBV）复制过程中的作用仍然知之甚少。在这项研究中，大量的miRNA拟态随着HBV的复制而转染至肝癌细胞株。我们注意到MicroRNAs- 1（miR - 1）的转染导致HBV复制显著增加，并伴有HBV转录的上调、抗原的表达以及子代的分泌。然而，生物信息学和荧光素酶报告分析显示miR - 1可能不是直接以HBV基因组为靶点，而是通过调控宿主基因的表达来提高HBV的复制。进一步的研究表明miR – 1可以通过增加法尼醇X受体α的表达来增强HBV核心启动子的转录活性。此外，miR - 1可将细胞周期阻滞于G1期，并通过攻击组蛋白脱乙酰基酶4和E2F转录因子5靶点来抑制细胞增殖。细胞基因表达谱分析表明miR - 1转染肝癌细胞形成了一种肝细胞分化表型。
结论：
MiR-1-调节了几个宿主基因表达以增强HBV的复制并逆转了癌症细胞表型，而这种表型显然有利于HBV复制。我们的发现为miRNA在HBV感染的宿主-病毒交互关系中的作用提供了新的观点。