Identification of the novel 3' UTR sequences of human IL-21 mRNA as potential targets of miRNAs.
Identification of the novel 3' UTR sequences of human IL-21 mRNA as potential targets of miRNAs.
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DOI：
10.1038/s41598-017-07853-x
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发表时间：
2017-08-10
影响因子：
4.6
通讯作者：
Miyajima A
中科院分区：
文献类型：
--
作者：
Enomoto Y;Takagi R;Naito Y;Kiniwa T;Tanaka Y;Hamada-Tsutsumi S;Kawano M;Matsushita S;Ochiya T;Miyajima A
乙肝病毒感染是世界范围内肝细胞癌的主要原因。然而，乙肝病毒逃离宿主免疫系统的策略在很大程度上仍不清楚。在这项研究中，我们检测了感染乙肝病毒的人肝细胞分泌的胞外小泡(EVS)。EV包括外切体，是含有蛋白质、mRNAs和microRNAs(MiRNAs)的纳米级囊泡，可以传递到不同的细胞。我们发现，肝细胞中104个EV相关的miRNAs在感染HBV2倍以上。然后，我们选择了那些可能与免疫调节有关的基因。其中，5个乙肝病毒诱导的miRNAs可能针对IL-21的3‘非编码区的多个序列，IL-21是一种诱导抗病毒免疫的细胞因子。此外，5个miRNAs分别抑制了人IL-21mRNA3‘端非编码区报告基因的表达。最后，克隆的人T细胞中IL-21的表达被5个miRNAs下调。总之，本研究确定了人IL-21mRNA的新的3‘非编码区序列和乙肝病毒诱导的EV-miRNAs的潜在结合位点。
Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma worldwide. However, the strategy of HBV to escape from the host immune system remains largely unknown. In this study, we examined extracellular vesicles (EVs) secreted from human hepatocytes infected with HBV. EVs includeing exosomes are nano-size vesicles with proteins, mRNAs, and microRNAs (miRNAs), which can be transmitted to different cells. We found that 104 EV associated miRNAs were increased in hepatocytes more than 2-fold by HBV infection. We then selected those that were potentially implicated in immune regulation. Among them, five HBV-induced miRNAs were found to potentially target multiple sequences in the 3′UTR of IL-21, a cytokine that induces anti-viral immunity. Moreover, expression of a reporter gene with the 3′ UTR of human IL-21 mRNA was suppressed by the five miRNAs individually. Finally, IL-21 expression in cloned human T cells was down-regulated by the five miRNAs. Collectively, this study identified the novel 3′ UTR sequences of human IL-21 mRNA and potential binding sites of HBV-induced EV-miRNAs.
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影响因子：
2.7
作者：
Chen HM;Liu HL;Yang YC;Cheng XL;Wang YF;Xing FF;Zhao YR
通讯作者：
Zhao YR
影响因子：
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作者：
Chiba M;Kimura M;Asari S
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作者：
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影响因子：
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作者：
Clayton, A;Tabi, Z
通讯作者：
Tabi, Z