Long Noncoding RNA High Expression in Hepatocellular Carcinoma Facilitates Tumor Growth Through Enhancer of Zeste Homolog 2 in Humans
Long Noncoding RNA High Expression in Hepatocellular Carcinoma Facilitates Tumor Growth Through Enhancer of Zeste Homolog 2 in Humans
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DOI：
10.1002/hep.24563
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发表时间：
2011-11-01
期刊：
影响因子：
13.5
通讯作者：
Sun, Shu-han
中科院分区：
文献类型：
--
作者：
Yang, Fu;Zhang, Ling;Sun, Shu-han
近年来，长非编码RNA(LncRNAs)在癌症生物学中具有重要的调控作用。然而，lncRNAs在乙肝病毒相关性肝细胞癌中的作用仍然很大程度上还不清楚。应用基因芯片技术鉴定与乙肝病毒相关的肝细胞癌和配对的瘤旁组织中差异表达的lncRNAs，并用实时定量聚合酶链式反应进行验证。对乙肝病毒相关性肝细胞癌患者的肝脏样本进行分析，以确定肝细胞癌中特异性差异表达的LncRNA高表达水平(称为LncRNA-HEIH)；使用Kaplan-Meier方法将数据与生存数据进行比较，并通过对数等级检验进行组间比较。通过体内和体外沉默和过表达来评价lncRNA的作用。LncRNA-HEIH在乙肝相关性肝细胞癌中的表达水平与复发密切相关，是影响患者生存的独立预后因素。我们还发现lncRNA-HEIH在G(0)/G(1)阻滞中起关键作用，并进一步证明了lncRNA-HEIH与Zust同源增强子2(EZH2)相关，并且这种关联是抑制EZH2靶基因所必需的。结论：综上所述，这些结果表明，lncRNA-HEIH是一种促进肿瘤进展的致癌lncRNA，并导致我们提出，lncRNA可能在肝细胞癌进展中起关键的调节中心作用。(《肝病》2011；54：1679-1689)
In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of lncRNAs to hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain largely unknown. Differentially expressed lncRNAs between HBV-related HCC and paired peritumoral tissues were identified by microarray and validated using quantitative real-time polymerase chain reaction. Liver samples from patients with HBV-related HCC were analyzed for levels of a specific differentially expressed lncRNA High Expression In HCC (termed lncRNA-HEIH); data were compared with survival data using the Kaplan-Meier method and compared between groups by the log-rank test. The effects of lncRNA-HEIH were assessed by silencing and overexpressing the lncRNA in vitro and in vivo. The expression level of lncRNA-HEIH in HBV-related HCC is significantly associated with recurrence and is an independent prognostic factor for survival. We also found that lncRNA-HEIH plays a key role in G(0)/G(1) arrest, and further demonstrated that lncRNA-HEIH was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Conclusions: Together, these results indicate that lncRNA-HEIH is an oncogenic lncRNA that promotes tumor progression and leads us to propose that lncRNAs may serve as key regulatory hubs in HCC progression. (HEPATOLOGY 2011;54:1679-1689)