Recurrently deregulated lncRNAs in hepatocellular carcinoma.

Recurrently deregulated lncRNAs in hepatocellular carcinoma.
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肝细胞癌中 lncRNA 经常失调。

DOI:
10.1038/ncomms14421
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发表时间:
2017-02-13
影响因子:
16.6
通讯作者:
Lu ZJ
Lu ZJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yang Y;Chen L;Gu J;Zhang H;Yuan J;Lian Q;Lv G;Wang S;Wu Y;Yang YT;Wang D;Liu Y;Tang J;Luo G;Li Y;Hu L;Sun X;Wang D;Guo M;Xi Q;Xi J;Wang H;Zhang MQ;Lu ZJ

文献摘要

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肝细胞癌(HCC)细胞常侵犯门静脉系统,继而发展为门静脉癌栓(PVTT)。长非编码RNA(LncRNAs)与肝细胞癌相关,但尚未对其与肝细胞癌转移的特异性关联进行全面的分析。在这里,通过分析来自20名肝癌患者的60个临床样本的RNA-SEQ数据,我们已经识别和表征了8,603个候选LncRNAs。917个反复失控的LncRNAs的表达模式与TCGA队列中的临床数据和已发表的肝癌数据相关。来自60个样本的匹配阵列数据显示,拷贝数变异(CNV)和DNA甲基化的改变导致了观察到的235个lncRNAs的反复去调控。许多反复失控的LncRNAs富含在与细胞黏附、免疫反应和代谢过程相关的共表达基因簇中。与转移相关的候选LncRNAs,如HAND2-AS1,通过基于RNAi的功能损失分析进一步验证。因此,我们提供了与肝细胞癌肿瘤发生和转移相关的功能性LncRNA和生物标记物的宝贵资源。长的非编码RNA与肝细胞癌有关,有些可作为预后标记物。在这里,作者通过分析20名患者的60个临床样本的RNA-SEQ,提供了与肝癌发生和转移相关的功能性LncRNAs和生物标记物的来源。
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis. Long noncoding-RNAs have been linked to hepatocellular carcinoma (HCC) and some can be used as prognostic markers. Here the authors, by analysing RNA-seq in 60 clinical samples from 20 patients, provide a resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.