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.

长的非编码RNA（lncRNAs）已牵涉到癌症的生物发生和预后。但是，我们仍然缺乏关于它们在神经胶质瘤进展过程中的功能的知识。在这项研究中，我们分析了907名II，III和IV级神经胶质瘤患者的lncRNA表达谱。揭示了神经胶质瘤进展过程中lncRNA的广泛动态表达，我们确定了33个癌基因-lncRNA和61个抑癌基因lncRNA。我们发现这些致癌lncRNAs的表达受等级特异性表达的转录因子调控。基于“有罪感”规则，我们预测了致癌lncRNA的潜在功能，并且这些lncRNA中的大多数都与癌症有关。特别是，我们发现CARD8-AS1在体外调节神经胶质瘤细胞系的转移潜能。综合临床信息，我们确定了神经胶质瘤中的12种保护性和8种风险性lncRNA（例如PWAR6和CARD8-AS1）。最后，鉴定出lncRNA基因功能模块与患者的存活有关。在独立的数据集中进一步验证了该模块签名的预测能力。我们的研究结果揭示了神经胶质瘤进展过程中的动态转录组过渡，表明lncRNA标记可能是有用的生物标志物，可能有助于我们进一步了解神经胶质瘤进展的分子机制。