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Exploring functions of long noncoding RNAs across multiple cancers through co-expression network

机译:通过共表达网络探索跨多种癌症的长非编码RNA的功能

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摘要

In contrast to protein-coding genes, long-noncoding RNAs (lncRNAs) are much less well understood, despite increasing evidence indicating a wide range of their biological functions, and possible roles in various cancers. Based on public RNA-seq datasets of four solid cancer types, we here utilize Weighted Correlation Network Analysis (WGCNA) to propose a strategy for exploring the functions of lncRNAs altered in more than two cancer types, which we call onco-lncRNAs. Results indicate that cancer-expressed lncRNAs show high tissue specificity and are weakly expressed, more so than protein-coding genes. Most of the 236 onco-lncRNAs we identified have not been reported to have associations with cancers before. Our analysis exploits co-expression network to reveal that onco-lncRNAs likely play key roles in the multistep development of human cancers, covering a wide range of functions in genome stability maintenance, signaling, cell adhesion and motility, morphogenesis, cell cycle, immune and inflammatory response. These observations contribute to a more comprehensive understanding of cancer-associated lncRNAs, while demonstrating a novel and efficient strategy for subsequent functional studies of lncRNAs.
机译:与蛋白质编码基因相反,尽管越来越多的证据表明其生物学功能范围广泛,并可能在各种癌症中起作用,但长期以来非编码RNA(lncRNA)的了解却少得多。基于四种实体癌类型的公共RNA-seq数据集,我们在这里利用加权相关网络分析(WGCNA)提出了一种策略,用于探索在两种以上癌症类型中被改变的lncRNA的功能,我们将其称为癌基因-lncRNA。结果表明,与蛋白编码基因相比,表达癌的lncRNAs具有较高的组织特异性且表达较弱。我们以前鉴定的236种癌基因-incRNAs中大多数都没有与癌症相关的报道。我们的分析利用共表达网络来揭示癌基因-lncRNA可能在人类癌症的多步发展中发挥关键作用,涵盖基因组稳定性维持,信号传导,细胞黏附和运动,形态发生,细胞周期,免疫和炎症反应。这些观察结果有助于对与癌症相关的lncRNA的更全面的了解,同时为随后的lncRNA功能研究展示了一种新颖而有效的策略。

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