Silencing of microRNA-122 enhances interferon-α signaling in the liver through regulating SOCS3 promoter methylation.
Silencing of microRNA-122 enhances interferon-α signaling in the liver through regulating SOCS3 promoter methylation.
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DOI：
10.1038/srep00637
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发表时间：
2012
影响因子：
4.6
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
--
作者：
Yoshikawa, Takeshi;Takata, Akemi;Otsuka, Motoyuki;Kishikawa, Takahiro;Kojima, Kentaro;Yoshida, Haruhiko;Koike, Kazuhiko
丙型肝炎病毒（HCV）感染是世界范围内慢性肝病的主要原因。虽然抗HCV的新药正在开发中，但目前的标准治疗主要由干扰素（IFN）组成。为了通过增强干扰素刺激反应元件（ISRE）介导的基因转录来改善对IFN治疗的反应，我们筛选了75种在肝细胞中高度表达的microRNA，以了解它们调节ISRE活性的能力。microRNA-122（miR 122）的过表达显著抑制ISRE活性。相反，miR 122功能的沉默通过降低细胞因子信号传导抑制因子3（SOCS 3）的表达来增强IFN诱导的ISRE活性。SOCS 3水平的降低不是由microRNA靶基因抑制介导的，而是由SOCS 3基因启动子甲基化增强介导的。总之，我们的数据，沿着miR 122的反义寡核苷酸也直接抑制HCV复制的事实，表明包括IFN和miR 122功能沉默的组合疗法可能是不久的将来有希望的治疗选择。
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. Although novel drugs against HCV are under development, the current standard therapy consists principally of interferon (IFN). To improve the response to IFN treatment by enhancing interferon-stimulated response element (ISRE)-mediated gene transcription, we screened 75 microRNAs highly expressed in hepatocytes for their ability to modulate ISRE activity. Overexpression of microRNA-122 (miR122) significantly suppressed ISRE activity. Conversely, silencing of miR122 function enhanced IFN-induced ISRE activity, by decreasing expression of suppressor of cytokine signaling 3 (SOCS3). This decrease in SOCS3 level was not mediated by microRNA target gene suppression, but rather by enhanced methylation at SOCS3 gene promoter. Taken together, our data, along with the fact that antisense oligonucleotides of miR122 also directly inhibit HCV replication, suggest that a combination therapy comprising IFN and silencing of miR122 function may be a promising therapeutic option in the near future.
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影响因子：
12.7
作者：
Akuta, Norio;Suzuki, Fumitaka;Kumada, Hiromitsu
通讯作者：
Kumada, Hiromitsu
影响因子：
29.4
作者：
Honda, Masao;Sakai, Akito;Kaneko, Shuichi
通讯作者：
Kaneko, Shuichi
影响因子：
29
作者：
Esau, C;Davis, S;Monia, BP
通讯作者：
Monia, BP
影响因子：
12.7
作者：
Akuta, Norio;Suzuki, Fumitaka;Kumada, Hiromitsu
通讯作者：
Kumada, Hiromitsu
DOI：
10.1126/science.1178178
发表时间：
2010-01-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lanford RE;Hildebrandt-Eriksen ES;Petri A;Persson R;Lindow M;Munk ME;Kauppinen S;Ørum H
通讯作者：
Ørum H