The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, The Key Laboratory of Neuro-informatics & Rehabilitation Engineering of Ministry of Civil Affairs, Xi'an, Shaanxi, P. R. China.
National Engineering Research Center for Healthcare Devices. Guangzhou, Guangdong, P.R. China.
PLoS Comput Biol. 2020 May 19;16(5):e1007793. doi: 10.1371/journal.pcbi.1007793. eCollection 2020 May.
Non-coding RNAs are fundamental to the competing endogenous RNA (CeRNA) hypothesis in oncology. Previous work focused on static CeRNA networks. We construct and analyze CeRNA networks for four sequential stages of lung adenocarcinoma (LUAD) based on multi-omics data of long non-coding RNAs (lncRNAs), microRNAs and mRNAs. We find that the networks possess a two-level bipartite structure: common competing endogenous network (CCEN) composed of an invariant set of microRNAs over all the stages and stage-dependent, unique competing endogenous networks (UCENs). A systematic enrichment analysis of the pathways of the mRNAs in CCEN reveals that they are strongly associated with cancer development. We also find that the microRNA-linked mRNAs from UCENs have a higher enrichment efficiency. A key finding is six microRNAs from CCEN that impact patient survival at all stages, and four microRNAs that affect the survival from a specific stage. The ten microRNAs can then serve as potential biomarkers and prognostic tools for LUAD.
非编码 RNA 是肿瘤竞争内源性 RNA (CeRNA) 假说的基础。以前的工作主要集中在静态 CeRNA 网络上。我们基于长非编码 RNA (lncRNA)、microRNA 和 mRNA 的多组学数据，构建和分析了肺腺癌 (LUAD) 四个连续阶段的 CeRNA 网络。我们发现这些网络具有两级二分结构: 由所有阶段不变的 microRNA 组成的常见竞争内源性网络 (CCEN) 和阶段依赖的、独特的竞争内源性网络 (UCEN)。对 CCEN 中 mRNAs 途径的系统富集分析表明，它们与癌症的发展密切相关。我们还发现，UCENs 中 microRNA 连接的 mRNAs 具有更高的富集效率。一个关键的发现是，CCEN 中的六个 microRNAs 影响所有阶段的患者生存，四个 microRNAs 影响特定阶段的生存。这十个 microRNAs 可以作为 LUAD 的潜在生物标志物和预后工具。
