Xu Juan, Li Yongsheng, Lu Jianping, Pan Tao, Ding Na, Wang Zishan, Shao Tingting, Zhang Jinwen, Wang Lihua, Li Xia
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin 150081, Heilongjiang Province, China
Nucleic Acids Res. 2015 Sep 30;43(17):8169-82. doi: 10.1093/nar/gkv853. Epub 2015 Aug 24.
Cross-talk between competitive endogenous RNAs (ceRNAs) through shared miRNAs represents a novel layer of gene regulation that plays important roles in the physiology and development of cancers. However, a global view of their system-level properties across various types of cancers is still unknown. Here, we constructed the mRNA related ceRNA-ceRNA interaction landscape across 20 cancer types by systematically analyzing molecular profiles of 5203 tumors and miRNA regulations. Our study highlights the conserved features shared by pan-cancer and higher similarity within similar origin cell type. Moreover, a core ceRNA network was identified. Function analysis identified a common theme of cancer hallmarks, however they exhibit phenotype-specific connectivity patterns. Besides, we found a marked rewiring in the ceRNA program between various cancers, and further revealed conserved and rewired network ceRNA hubs in each cancer, which were tensely competitive interactions to constitute conserved and cancer-specific modules. By providing mechanistic linkage between known cancer miRNAs, their mediated ceRNA-ceRNA interactions, and the associations with known cancer hallmarks, the inferred cancer ceRNA-ceRNA interaction landscape will serve as a powerful public resource for further biological discoveries of tumorigenesis.
竞争性内源RNA（ceRNA）通过共享的微小RNA（miRNA）进行的相互作用代表了基因调控的一个新层面，在癌症的生理和发展过程中发挥着重要作用。然而，它们在各种癌症类型中的系统层面特性的全局视图仍然未知。在此，我们通过系统分析5203个肿瘤的分子谱和miRNA调控，构建了涵盖20种癌症类型的与mRNA相关的ceRNA-ceRNA相互作用图谱。我们的研究突出了泛癌共有的保守特征以及相似起源细胞类型内更高的相似性。此外，还鉴定出了一个核心ceRNA网络。功能分析确定了癌症特征的一个共同主题，然而它们表现出表型特异性的连接模式。此外，我们发现不同癌症之间ceRNA程序存在显著的重新布线，并进一步揭示了每种癌症中保守和重新布线的网络ceRNA枢纽，它们是构成保守和癌症特异性模块的激烈竞争相互作用。通过提供已知癌症miRNA之间的机制联系、它们介导的ceRNA-ceRNA相互作用以及与已知癌症特征的关联，推断出的癌症ceRNA-ceRNA相互作用图谱将成为肿瘤发生进一步生物学发现的强大公共资源。
