The search for new biomarkers and drug targets for hepatocellular carcinoma (HCC) has spurred an interest in long non-coding RNAs (lncRNAs), often proposed as oncogenes or tumor suppressors. Furthermore, lncRNA expression patterns can bring insights into the global de-regulation of cellular machineries in tumors. Here, we examine lncRNAs in a large HCC cohort, comprising RNA-seq data from paired tumor and adjacent tissue biopsies from 114 patients. We find that numerous lncRNAs are differentially expressed between tumors and adjacent tissues and between tumor progression stages. Although we find strong differential expression for most lncRNAs previously associated with HCC, the expression patterns of several prominent HCC-associated lncRNAs disagree with their previously proposed roles. We examine the genomic characteristics of HCC-expressed lncRNAs and reveal an enrichment for repetitive elements among the lncRNAs with the strongest expression increases in advanced-stage tumors. This enrichment is particularly striking for lncRNAs that overlap with satellite repeats, a major component of centromeres. Consistently, we find increased non-coding RNA transcription from centromeres in tumors, in the majority of patients, suggesting that aberrant centromere activation takes place in HCC.

中文翻译：

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LncRNA分析显示肝细胞癌中非编码着丝粒转录本水平升高

对肝细胞癌（HCC）的新生物标志物和药物靶标的搜寻激发了人们对长非编码RNA（lncRNA）的兴趣，通常建议将其作为致癌基因或抑癌基因。此外，lncRNA表达模式可以为深入了解肿瘤中细胞机制的失调带来深刻见解。在这里，我们检查了一个大型HCC队列中的lncRNA，其中包括来自成对肿瘤的RNA-seq数据和来自114位患者的相邻组织活检。我们发现许多lncRNAs在肿瘤和相邻组织之间以及肿瘤进展阶段之间差异表达。尽管我们发现以前与HCC相关的大多数lncRNA都有很强的差异表达，但几种与HCC相关的著名lncRNA的表达方式与它们先前提出的角色不同。我们检查了表达HCC的lncRNA的基因组特征，并揭示了在晚期肿瘤中表达最强的lncRNA中重复元素的富集。对于与卫星重复（着丝粒的主要组成部分）重叠的lncRNA，这种富集尤其显着。一致地，我们发现在大多数患者中，肿瘤中着丝粒的非编码RNA转录增加，提示在肝癌中发生着丝粒着丝异常。