MicroRNA-125b-5p mediates post-transcriptional regulation of hepatitis B virus replication via the LIN28B/let-7 axis
MicroRNA-125b-5p mediates post-transcriptional regulation of hepatitis B virus replication via the LIN28B/let-7 axis
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DOI：
10.1080/15476286.2017.1293770
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发表时间：
2017-01-01
期刊：
影响因子：
4.1
通讯作者：
Lu, Mengji
中科院分区：
文献类型：
--
作者：
Deng, Wanyu;Zhang, Xiaoyong;Lu, Mengji
MicroRNAs （miRNAs）能够调节乙型肝炎病毒（HBV）的复制，并在HBV感染的发病机制中发挥重要作用。最近，我们发现血清miR-125b-5p水平与HBV DNA水平和肝脏坏死炎症相关。在本研究中，我们研究了miR-125b-5p如何在不同的步骤中调节HBV复制，包括病毒转录、组装和病毒粒子产生，并研究了潜在的机制。我们发现miR-125b-5p过表达增加HBV复制而不改变HBV转录。这是首次证明miRNA转录后调控HBV复制。相反，转染miR-125b-5p抑制剂导致肝癌细胞中HBV复制的下调。此外，miR-125b-5p抑制视网膜母细胞瘤蛋白的磷酸化，阻断肝癌细胞系G1/S期的细胞周期进程。我们的研究结果表明，某些mirna能够在G1期阻止细胞周期，并可能增加HBV复制。RNA测序揭示了miR-125b-5p调控的几种肝脏特异性代谢途径，也发现miR-125b-5p抑制LIN28B并诱导let-7家族成员。其他数据表明，miR-125b-5p靶向LIN28B/let-7轴，在转录后步骤刺激HBV复制。
MicroRNAs (miRNAs) are able to modulate hepatitis B virus (HBV) replication and play an important role in the pathogenesis of HBV infection. Recently, we have identified that serum miR-125b-5p levels correlated with HBV DNA levels and liver necroinflammation. In the present study, we addressed how miR-125b-5p regulated HBV replication at the different steps, inclduing viral transcription, assembly, and virion production and investigated the underlying mechanisms. We found that miR-125b-5p overexpression increased HBV replication without altering HBV transcription. This is the first demonstration of post-transcriptional miRNA regulation of HBV replication. In contrast, transfection of miR-125b-5p inhibitor resulted in downregulation of HBV replication in hepatoma cells. Further, miR-125b-5p inhibited the phosphorylation of retinoblastoma protein and blocked cell cycle progression at the G1/S phase in hepatoma cell lines. Our results indicate that certain miRNAs are able to arrest the cell cycle at G1 phase and may increase HBV replication. RNA sequencing revealed several liver-specific metabolic pathways regulated by miR-125b-5p, which was also found to suppress LIN28B and induce let-7 family members. Additional data demonstrated that miR-125b-5p targeted the LIN28B/let-7 axis to stimulate HBV replication at a post-transcriptional step.