Zhang Xiao-Qin, Kiang Karrie Mei-Yee, Wang Yue-Chun, Pu Jenny Kan-Suen, Ho Amy, Cheng Stephen Yin, Lee Derek, Zhang Ping-De, Chen Jia-Jing, Lui Wai-Man, Fung Ching-Fai, Leung Gilberto Ka-Kit
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Department of Physiology, Medicine College of Jinan University, Guangzhou, China.
J Neurooncol. 2015 Nov;125(2):253-63. doi: 10.1007/s11060-015-1916-9. Epub 2015 Sep 3.
Isocitrate dehydrogenase 1 (IDH1) mutation is an important prognostic marker in glioma. However, its downstream effect remains incompletely understood. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis in a number of human malignancies, including glioma. Here, we investigated whether and how lncRNA expression profiles would differ between gliomas with or without IDH1 mutation. By using our previously reported lncRNA mining approach, we performed lncRNA profiling in three public glioma microarray datasets. The differential lncRNA expression analysis was then conducted between mutant-type and wild-type IDH1 glioma samples. Comparison analysis identified 14 and 9 lncRNA probe sets that showed significantly altered expressions in astrocytic and oligodendroglial tumors, respectively (fold change ≥ 1.5, false discovery rate ≤ 0.1). Moreover, the differential expressions of these lncRNAs could be confirmed in the independent testing sets. Functional exploration of the lncRNAs by analyzing the lncRNA-protein interactions revealed that these IDH1 mutation-associated lncRNAs were involved in multiple tumor-associated cellular processes, including metabolism, cell growth and apoptosis. Our data suggest the potential roles of lncRNA in gliomagenesis, and may help to understand the pathogenesis of gliomas associated with IDH1 mutation.
异柠檬酸脱氢酶1（IDH1）突变是胶质瘤的一个重要预后标志物。然而，其下游效应仍未完全明确。长链非编码RNA（lncRNA）正逐渐成为包括胶质瘤在内的多种人类恶性肿瘤发生发展的重要调节因子。在此，我们研究了lncRNA表达谱在IDH1突变型和野生型胶质瘤之间是否存在差异以及如何存在差异。通过使用我们先前报道的lncRNA挖掘方法，我们在三个公开的胶质瘤微阵列数据集中进行了lncRNA分析。然后在突变型和野生型IDH1胶质瘤样本之间进行差异lncRNA表达分析。比较分析确定了14个和9个lncRNA探针集，它们分别在星形细胞瘤和少突胶质细胞瘤中显示出显著改变的表达（倍数变化≥1.5，错误发现率≤0.1）。此外，这些lncRNA的差异表达可以在独立测试集中得到证实。通过分析lncRNA与蛋白质的相互作用对lncRNA进行功能探索，结果表明这些与IDH1突变相关的lncRNA参与了多个与肿瘤相关的细胞过程，包括代谢、细胞生长和凋亡。我们的数据表明lncRNA在胶质瘤发生中的潜在作用，并可能有助于理解与IDH1突变相关的胶质瘤的发病机制。
