Yang Shuang, Ning Qianqian, Zhang Guobin, Sun Hong, Wang Zhen, Li Yixue
Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Center for Bioinformation Technology, Shanghai, China.
Oncotarget. 2016 Dec 27;7(52):85728-85740. doi: 10.18632/oncotarget.13828.
Increasing evidence has indicated that lncRNAs acting as competing endogenous RNAs (ceRNAs) play crucial roles in tumorigenesis, metastasis and diagnosis of cancer. However, the function of lncRNAs as ceRNAs involved in esophageal squamous cell carcinoma (ESCC) is still largely unknown. In this study, clinical implications of two intrinsic subtypes of ESCC were identified based on expression profiles of lncRNA and mRNA. ESCC subtype-specific differential co-expression networks between mRNAs and lncRNAs were constructed to reveal dynamic changes of their crosstalks mediated by miRNAs during tumorigenesis. Several well-known cancer-associated lncRNAs as the hubs of the two networks were firstly proposed in ESCC. Based on the ceRNA mechanism, we illustrated that the"loss" of miR-186-mediated PVT1-mRNA and miR-26b-mediated LINC00240-mRNA crosstalks were related to the two ESCC subtypes respectively. In addition, crosstalks between LINC00152 and EGFR, LINC00240 and LOX gene family were identified, which were associated with the function of "response to wounding" and "extracellular matrix-receptor interaction". Furthermore, functional cooperation of multiple lncRNAs was discovered in the two differential mRNA-lncRNA crosstalk networks. These together systematically uncovered the roles of lncRNAs as ceRNAs implicated in ESCC.
越来越多的证据表明，作为竞争性内源RNA（ceRNA）的长链非编码RNA（lncRNA）在肿瘤发生、转移和癌症诊断中发挥着关键作用。然而，lncRNA作为ceRNA在食管鳞状细胞癌（ESCC）中的功能仍 largely未知。在本研究中，基于lncRNA和mRNA的表达谱鉴定了ESCC的两种内在亚型的临床意义。构建了mRNA和lncRNA之间的ESCC亚型特异性差异共表达网络，以揭示它们在肿瘤发生过程中由miRNA介导的相互作用的动态变化。在ESCC中首次提出了几种著名的与癌症相关的lncRNA作为两个网络的枢纽。基于ceRNA机制，我们阐明了miR-186介导的PVT1-mRNA和miR-26b介导的LINC00240-mRNA相互作用的“缺失”分别与两种ESCC亚型相关。此外，还鉴定了LINC00152与EGFR、LINC00240与LOX基因家族之间的相互作用，这与“对损伤的反应”和“细胞外基质-受体相互作用”的功能相关。此外，在两个差异mRNA-lncRNA相互作用网络中发现了多个lncRNA的功能合作。这些共同系统地揭示了lncRNA作为ceRNA在ESCC中的作用。
