Construction of lncRNA-mediated ceRNA network to reveal clinically relevant lncRNA biomarkers in glioblastomas

Zan,Xiang-Yang; Li,Luo

doi:10.3892/ol.2019.10114

Construction of lncRNA-mediated ceRNA network to reveal clinically relevant lncRNA biomarkers in glioblastomas

Authors:
- Xiang-Yang Zan
- Luo Li
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Affiliations: Department of Neurosurgery, Affiliated Traditional Chinese Medical Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China
Published online on: March 5, 2019 https://doi.org/10.3892/ol.2019.10114
Pages: 4369-4374
Copyright: © Zan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cross-talk between competing endogenous RNAs (ceRNAs) play key roles in tumor development. In this study, we performed exon-level expression profiling on 26 glioblastomas (GBMs) and 6 controls to identify long non-coding RNAs (lncRNAs) of GBM initiation and progression using lncRNA-mediated ceRNA network (LMCN). The mRNA and lncRNA expression data, as well as miRNA-target interactions were firstly collected. Then, we used hypergeometric test to detect the lncRNA-mRNA interactions, followed by the construction of LMCN based on Pearson correlation coefficient. With the goal of investigation of the network organization, degree distribution of LMCN was performed. Next, the synergistic, competing lncRNA modules were identified using jActiveModule plug-in of Cytoscape. Moreover, we implemented the pathway analysis for its mRNAs in the module to explore the functions of significant lncRNAs. Using the criteria of degrees >50, 8 hub genes were identified, including EPB41L4A-AS1, ZRANB2-AS2, XIST, HOTAIR, TRAF3IP2-AS1, TPT1-AS1, PVT1 and DLG1‑AS1. Furthermore, 1 synergistic, competitive module was identified. In this module, lncRNAs XIST and PVT1 were also the hubs in the synergistic, competing lncRNA module. Functional annotation demonstrated that 5 pathways were identified, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and mTOR signaling pathway. We have successfully identified several hubs (such as XIST and PVT1) and significant pathways (for instance, cytokine‑cytokine receptor interaction, and neuroactive ligand-receptor interactions) for GBM via establishing the LMCN. These findings might offer potential biomarkers to early diagnose, and predict GBM prognosis in the future.

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