Construction of differential mRNA-lncRNA crosstalk networks based on ceRNA hypothesis uncover key roles of lncRNAs implicated in esophageal squamous cell carcinoma

// Shuang Yang 1,3,* , Qianqian Ning 1,3,* , Guobin Zhang 2 , Hong Sun 4 , Zhen Wang 2 and Yixue Li 1,2,3,5 1 Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China 2 Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 3 Shanghai Center for Bioinformation Technology, Shanghai, China 4 Biomedical Information Research Center, Children’s Hospital of Shanghai 5 Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Hong Sun, email: // Zhen Wang, email: // Yixue Li, email: // Keywords : intrinsic subtype; competing endogenous RNA network; biomarker; lncRNA; ESCC; Pathology Section Received : September 24, 2016 Accepted : November 18, 2016 Published : December 09, 2016 Abstract 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.