Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Sci Rep. 2016 Oct 13;6:34740. doi: 10.1038/srep34740.
Hepatitis B virus (HBV) is a major human pathogen. In this study, we found that miR-204 and miR-1236 were down-regulated in HBV-producing cells, and each could suppress HBV replication. Using a bioinformatic approach and a reporter assay, we identified miR-1236, which can reduce HBV replication and protein production by directly targeting at HBV specific mRNA. In contrast, miR-204 was identified by a microarray approach, and had no effect on HBV RNA and protein production. Surprisingly, miR-204 could inhibit HBV pregenomic RNA encapsidation and capsid assembly. We further demonstrated that HBV suppressed miR-204 expression via activating a host transcription factor STAT3. We established a positive feed-forward loop between HBV, miR-204 and STAT3. Interestingly, miR-204 has been considered as a tumor suppressor in some literature. Since the risk for hepatocellular carcinoma (HCC) is significantly increased in chronic HBV patients, it is possible that chronic suppression of miR-204 by HBV contributes to HCC incidence. Both miR-204 and miR-1236 might be useful for developing new therapeutics against HBV.
乙型肝炎病毒（HBV）是一种主要的人类病原体。在这项研究中，我们发现产生 HBV 的细胞中 miR-204 和 miR-1236 下调，且两者均可抑制 HBV 复制。我们采用生物信息学方法和报告基因检测，发现 miR-1236 可通过直接靶向 HBV 特异性 mRNA 降低 HBV 复制和蛋白产生。相比之下，miR-204 通过微阵列方法鉴定，对 HBV RNA 和蛋白产生没有影响。令人惊讶的是，miR-204 可抑制 HBV 前基因组 RNA 包裹和衣壳组装。我们进一步证实 HBV 通过激活宿主转录因子 STAT3 抑制 miR-204 的表达。我们建立了 HBV、miR-204 和 STAT3 之间的正反馈环。有趣的是，miR-204 在一些文献中被认为是一种肿瘤抑制因子。由于慢性 HBV 患者肝癌（HCC）的风险显著增加，因此 HBV 慢性抑制 miR-204 可能导致 HCC 发生率增加。miR-204 和 miR-1236 都可能有助于开发针对 HBV 的新治疗方法。
