Specific delivery of microRNA93 into HBV-replicating hepatocytes downregulates protein expression of liver cancer susceptible gene MICA.
Specific delivery of microRNA93 into HBV-replicating hepatocytes downregulates protein expression of liver cancer susceptible gene MICA.
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DOI：
10.18632/oncotarget.2143
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Koike K
中科院分区：
文献类型：
--
作者：
Ohno M;Otsuka M;Kishikawa T;Shibata C;Yoshikawa T;Takata A;Muroyama R;Kowatari N;Sato M;Kato N;Kuroda S;Koike K
慢性B型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要病因。迄今为止，缺乏支持HBV感染和复制的有效体外系统一直是HBV研究的主要限制。虽然原代人肝细胞支持完整的HBV生命周期，但其有限的可用性和基因转导的困难仍然是个问题。在这里，我们使用从人源化嵌合uPA/SCID小鼠分离的人原代肝细胞作为有效来源。这些肝细胞在体外支持HBV复制。基于HBV感染肝细胞中mRNA和microRNA（miRNA）表达水平的分析，在HBV感染期间，miRNA 93显著下调。MiRNA 93对调节云母蛋白的表达水平至关重要，MICA蛋白是HBV诱导的HCC易感性的决定因素。使用由HBV包膜L蛋白组成的生物纳米帽在HBV感染的肝细胞中外源性添加miRNA 93恢复了上清液中云母蛋白的表达水平。这些结果表明，使用生物纳米碳靶向HBV感染的肝细胞的miRNA 93对可溶性云母蛋白水平的挽救性抑制可能有助于通过改变失调的miRNA 93表达来预防HBV诱导的HCC。
Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). To date, the lack of efficient in vitro systems supporting HBV infection and replication has been a major limitation of HBV research. Although primary human hepatocytes support the complete HBV life cycle, their limited availability and difficulties with gene transduction remain problematic. Here, we used human primary hepatocytes isolated from humanized chimeric uPA/SCID mice as efficient sources. These hepatocytes supported HBV replication in vitro. Based on analyses of mRNA and microRNA (miRNA) expression levels in HBV-infected hepatocytes, miRNA93 was significantly downregulated during HBV infection. MiRNA93 is critical for regulating the expression levels of MICA protein, which is a determinant for HBV-induced HCC susceptibility. Exogenous addition of miRNA93 in HBV-infected hepatocytes using bionanocapsules consisted of HBV envelope L proteins restored MICA protein expression levels in the supernatant. These results suggest that the rescued suppression of soluble MICA protein levels by miRNA93 targeted to HBV-infected hepatocytes using bionanocapsules may be useful for the prevention of HBV-induced HCC by altering deregulated miRNA93 expression.
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影响因子：
2.9
作者：
Mittal S;El-Serag HB
通讯作者：
El-Serag HB
DOI：
10.1124/jpet.103.061713
发表时间：
2004-04-01
影响因子：
3.5
作者：
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de Morais, SMF
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13.5
作者：
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通讯作者：
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DOI：
10.1016/s0006-291x(02)02861-9
发表时间：
2003-01-10
影响因子：
3.1
作者：
Otsuka, M;Aizaki, H;Seki, N
通讯作者：
Seki, N
DOI：
10.1111/j.1440-1746.2011.06979.x
发表时间：
2012-04-01
影响因子：
4.1
作者：
Pan, Xiao-Ben;Ma, Hui;Wei, Lai
通讯作者：
Wei, Lai