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人肝癌细胞中叉头框蛋白A对乙型肝炎病毒复制的负调控

Negative regulation of hepatitis B virus replication by forkhead box protein A in human hepatoma cells.

作者信息

Okumura Nobuaki, Ikeda Masanori, Satoh Shinya, Dansako Hiromichi, Sugiyama Masaya, Mizokami Masashi, Kato Nobuyuki

机构信息

Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; Department of Persistent and Oncogenic Viruses, Center for Chronic Viral Disease, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; Department of Persistent and Oncogenic Viruses, Center for Chronic Viral Disease, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

出版信息

FEBS Lett. 2015 Apr 28;589(10):1112-8. doi: 10.1016/j.febslet.2015.03.022. Epub 2015 Mar 30.

Abstract

Hepatitis B virus (HBV) replication is controlled by liver-enriched transcriptional factors, including forkhead box protein A (FOXA) members. Here, we found that FOXA members are directly and indirectly involved in HBV replication in human hepatic cells. HBV replication was elevated in HuH-7 treated with individual FOXA members-specific siRNA. Reciprocally, the downregulation of HBV replication was observed in FOXA-induced HuH-7. However, the mechanism of downregulation is different among FOXA members at the level of HBV RNA transcription, such as precore/pg RNA and 2.1 kb RNA. In addition, FOXA1 and FOXA2 suppressed nuclear hormone receptors, such as HNF4α, that are related to HBV replication.

摘要

乙型肝炎病毒(HBV)的复制受肝脏富集转录因子的控制,包括叉头框蛋白A(FOXA)家族成员。在此,我们发现FOXA家族成员直接或间接参与人类肝细胞中的HBV复制。用单个FOXA家族成员特异性siRNA处理的HuH-7细胞中,HBV复制增加。相反,在FOXA诱导的HuH-7细胞中观察到HBV复制下调。然而,在HBV RNA转录水平,如前核心/pg RNA和2.1 kb RNA,FOXA家族成员下调HBV复制的机制有所不同。此外,FOXA1和FOXA2抑制了与HBV复制相关的核激素受体,如肝细胞核因子4α(HNF4α)。

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