Characterization of Transcriptome Transition Associates Long Noncoding RNAs with Glioma Progression

Abstract

Long noncoding RNAs (lncRNAs) have been implicated in cancer biogenesis and prognosis. However, we still lack knowledge on their function during glioma progression. In this study, we analyzed the lncRNA expression profile across 907 glioma patients in grades II, III, and IV. Widespread dynamic expression of lncRNAs during glioma progression was revealed, and we identified 33 onco-lncRNAs and 61 tumor suppressor lncRNAs. We found that the expression of these oncogenic lncRNAs is regulated by grade-specific expressed transcription factors. Based on the “guilt by association” rule, we predicted the potential functions of oncogenic lncRNAs, and the majority of these lncRNAs are involved in cancer hallmarks. Especially we found that CARD8-AS1 regulates the metastatic potential of glioma cell lines in vitro. Integrating clinical information, we identified the 12 protective and 8 risk lncRNAs (such as PWAR6 and CARD8-AS1) in glioma. Finally, an lncRNA-gene functional module was identified to be associated with the survival of patients. The predictive ability of this module signature was further validated in an independent dataset. Our results revealed the dynamic transcriptome transition during glioma progression, indicating that the lncRNA signature could be a useful biomarker that may improve upon our understanding of the molecular mechanisms underlying glioma progression. Keywords: glioma progression, long noncoding RNA, transcription regulation, cancer hallmark, survival