Differential MicroRNA Expression Between Hepatitis B and Hepatitis C Leading Disease Progression to Hepatocellular Carcinoma
Differential MicroRNA Expression Between Hepatitis B and Hepatitis C Leading Disease Progression to Hepatocellular Carcinoma
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DOI：
10.1002/hep.22749
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发表时间：
2009-04-01
期刊：
影响因子：
13.5
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
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作者：
Ura, Shunsuke;Honda, Masao;Kaneko, Shuichi
microRNA（miRNA）在包括感染和癌症在内的多种疾病的病理学中起着重要作用。采用实时聚合酶链反应，我们测量了188个miRNA的表达，从12例B肝炎病毒（HBV）相关的肝细胞癌（HCC）和14例丙型肝炎病毒（HCV）相关的HCC患者，包括背景肝组织和正常肝组织从9例患者。通过互补DNA微阵列分析相同组织中的整体基因表达，以检查差异表达的miRNAs是否可以调节其靶基因。对差异表达的miRNA的详细分析显示两种类型的miRNA，一种与HBV和HCV感染相关（n = 19），另一种与肝病阶段相关（n = 3 1）。利用感染相关的miRNAs对靶基因进行通路分析，发现HBV感染肝脏中与细胞死亡、DNA损伤、重组和信号转导相关的通路被激活，而与免疫应答、抗原呈递、细胞周期、蛋白酶体和脂质代谢相关的通路在HCV感染肝脏中被激活。肝脏中感染相关miRNA表达的差异与Huh7.5细胞中观察到的差异显著相关，其中感染性HBV或HCV克隆复制。在与疾病状态相关的31种miRNAs中，17种在HCC中下调，其上调癌症相关途径，如细胞周期，粘附，蛋白水解，转录和翻译; 6种在HCC中上调，其下调抗肿瘤免疫应答。结论：miRNA是HBV和HCV感染以及肝病进展的重要介质，因此可能成为潜在的治疗靶分子。（《肝脏病学》2009年;49：1098-1112。）
MicroRNA (miRNA) plays an important role in the pathology of various diseases, including infection and cancer. Using real-time polymerase chain reaction, we measured the expression of 188 miRNAs in liver tissues obtained from 12 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 14 patients with hepatitis C virus (HCV)-related HCC, including background liver tissues and normal liver tissues obtained from nine patients. Global gene expression in the same tissues was analyzed via complementary DNA microarray to examine whether the differentially expressed miRNAs could regulate their target genes. Detailed analysis of the differentially expressed miRNA revealed two types of miRNA, one associated with HBV and HCV infections (n = 19), the other with the stage of liver disease (n = 3 1). Pathway analysis of targeted genes using infection-associated miRNAs revealed that the pathways related to cell death, DNA damage, recombination, and signal transduction were activated in HBV-infected liver, and those related to immune response, antigen presentation, cell cycle, proteasome, and lipid metabolism were activated in HCV-infected liver. The differences in the expression of infection-associated miRNAs in the liver correlated significantly with those observed in Huh7.5 cells in which infectious HBV or HCV clones replicated. Out of the 31 miRNAs associated with disease state, 17 were down-regulated in HCC, which up-regulated cancer-associated pathways such as cell cycle, adhesion, proteolysis, transcription, and translation; 6 miRNAs were up-regulated in HCC, which down-regulated anti-tumor immune response. Conclusion: miRNAs are important mediators of HBV and HCV infection as well as liver disease progression, and therefore could be potential therapeutic target molecules. (HEPATOLOGY 2009;49:1098-1112.)