Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function

A growing number of gene-centric studies have highlighted the emerging significance of lncRNAs in cancer. However, these studies primarily focus on a single cancer type. Therefore, we conducted a pan-cancer analysis of lncRNAs comparing tumor and matched normal expression levels using RNA-Seq data from ∼ 3,000 patients in 8 solid tumor types. While the majority of differentially expressed lncRNAs display tissue-specific expression we discovered 229 lncRNAs with outlier or differential expression across multiple cancers, which we refer to as 'onco-lncRNAs'. Due to their consistent altered expression, we hypothesize that these onco-lncRNAs may have conserved oncogenic and tumor suppressive functions across cancers. To address this, we associated the onco-lncRNAs in biological processes based on their co-expressed protein coding genes. To validate our predictions, we experimentally confirmed cell growth dependence of 2 novel oncogenic lncRNAs, onco-lncRNA-3 and onco-lncRNA-12, and a previously identified lncRNA CCAT1. Overall, we discovered lncRNAs that may have broad oncogenic and tumor suppressor roles that could significantly advance our understanding of cancer lncRNA biology.越来越多以基因为中心的研究凸显了长链非编码RNA（long non-coding RNA，lncRNA）在癌症中的新兴意义。然而，此类研究大多仅针对单一癌症类型展开。为此，我们针对8种实体瘤类型中约3000名患者的RNA测序（RNA-Seq）数据，开展了长链非编码RNA的泛癌分析，对比肿瘤组织与配对正常组织的表达水平。尽管大多数差异表达的长链非编码RNA呈现组织特异性表达模式，但我们在多种癌症中发现了229个存在异常或差异表达的长链非编码RNA，并将其命名为“致癌长链非编码RNA（onco-lncRNAs）”。鉴于这些致癌长链非编码RNA的表达改变具有一致性，我们推测其在不同癌症中可能发挥保守的致癌或抑癌功能。为验证这一推测，我们基于致癌长链非编码RNA的共表达蛋白编码基因，将其关联至相应的生物学过程。为验证我们的预测结果，我们通过实验证实了2种新型致癌长链非编码RNA——onco-lncRNA-3与onco-lncRNA-12——以及此前已被发现的长链非编码RNA CCAT1的细胞生长依赖性。综上，我们发现了一批可能兼具广谱致癌与抑癌功能的长链非编码RNA，这将极大推动我们对癌症相关长链非编码RNA生物学的认知。