期刊
ONCOTARGET
卷 7, 期 27, 页码 41737-41747出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9569
关键词
lncRNA; ceRNA network; topology; prognostic biomarker; synergistic regulation
资金
- National High Technology Research and Development Program of China [863 Program] [2014AA021102]
- National Program on Key Basic Research Project [973 Program] [2014CB910504]
- National Natural Science Foundation of China [91439117, 61473106, 31401090]
- Yu Weihan Outstanding Youth Training Fund of Harbin Medical University
Glioblastoma multiforme (GBM) is a highly malignant brain tumor associated with a poor prognosis. Cross-talk between competitive endogenous RNAs (ceRNAs) plays a critical role in tumor development and physiology. In this study, we present a multi-step computational approach to construct a functional GBM long non-coding RNA (lncRNA)-mediated ceRNA network (LMCN) by integrating genome-wide lncRNA and mRNA expression profiles, miRNA-target interactions, functional analyses, and clinical survival analyses. LncRNAs in the LMCN exhibited specific topological features consistent with a regulatory association with coding mRNAs across GBM pathology. We determined that the lncRNA MCM3AP-AS was involved in RNA processing and cell cycle-related functions, and was correlated with patient survival. MCM3AP-AS and MIR17HG acted synergistically to regulate mRNAs in a network module of the competitive LMCN. By integrating the expression profile of this module into a risk model, we stratified GBM patients in both the The Cancer Genome Atlas and an independent GBM dataset into distinct risk groups. Finally, survival analyses demonstrated that the lncRNAs and network module are potential prognostic biomarkers for GBM. Thus, ceRNAs could accelerate biomarker discovery and therapeutic development in GBM.
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