Department of Neurology, Hadassah Hebrew University Medical Centre, Leslie and Michael Gaffin Centre for Neuro-Oncology, Jerusalem, Israel.
Neuro Oncol. 2010 May;12(5):422-33. doi: 10.1093/neuonc/nop061. Epub 2010 Feb 8.
Gliomas express many genes that play a role in neural precursor cells (NPCs), but no direct comparison between glioma and stem cell (SC) gene expression profiles has been performed. To investigate the similarities and differences between gliomas and SCs, we compared the microRNA (miRNA) expression signatures of glial tumors, embryonic SCs (ESCs), NPCs, and normal adult brains from both human and mouse tissues. We demonstrated that both human gliomas (regardless of their grade) and methylcholanthrene-induced mouse glioma shared an miRNA expression profile that is reminiscent of NPCs. About half of the miRNAs expressed in the shared profile clustered in seven genomic regions susceptible to genetic/epigenetic alterations in various cancers. These clusters comprised the miR17 family, mir183-182, and the SC-specific clusters mir367-302 and mir371-373, which are upregulated in gliomas, ESCs, and NPCs. The bipartite cluster of 7 + 46 miRNAs on chromosome 14q32.31, which might represent the largest tumor suppressor miRNA cluster, was downregulated in the shared expression profile. This study provides the first evidence for association between these clusters and gliomas. Despite the broad similarity in the miRNA expression profiles, 15 miRNAs showed disparate expression between SC and gliomas. Ten miRNAs belong to the 2 SC-specific clusters and the remaining (mir135b, mir141, mir205, mir200C, and mir301a) have been previously shown to associate with malignancies. Our finding showed that all gliomas displayed NPC-like miRNA signatures, which may have implications for studies of glioma origins. Furthermore, careful study of the 15 miRNAs that differ in expression between SCs and gliomas, particularly those 5 that are not SC-specific, may enhance our understanding of gliomagenesis.
神经胶质瘤表达许多在神经前体细胞(NPC)中起作用的基因,但尚未对神经胶质瘤和干细胞(SC)基因表达谱进行直接比较。为了研究神经胶质瘤和 SC 之间的相似性和差异性,我们比较了胶质肿瘤、胚胎干细胞(ESC)、NPC 和来自人类和小鼠组织的正常成年大脑的 microRNA(miRNA)表达特征。我们证明,无论是人类的低级别还是高级别神经胶质瘤,还是甲基胆蒽诱导的小鼠神经胶质瘤,其 miRNA 表达谱都与 NPC 相似。在共有表达谱中表达的 miRNA 约有一半聚类在七个基因组区域,这些区域易受到各种癌症中遗传/表观遗传改变的影响。这些聚类包括 miR17 家族、mir183-182 和 SC 特异性聚类 mir367-302 和 mir371-373,它们在神经胶质瘤、ESC 和 NPC 中上调。14q32.31 染色体上的二分聚类 7 + 46 miRNAs 可能代表最大的肿瘤抑制 miRNA 聚类,在共有表达谱中下调。这项研究首次提供了这些聚类与神经胶质瘤之间关联的证据。尽管 miRNA 表达谱广泛相似,但 15 个 miRNA 在 SC 和神经胶质瘤之间表达不同。10 个 miRNA 属于 2 个 SC 特异性聚类,其余(mir135b、mir141、mir205、mir200C 和 mir301a)先前与恶性肿瘤有关。我们的研究结果表明,所有神经胶质瘤都表现出 NPC 样 miRNA 特征,这可能对神经胶质瘤起源的研究具有重要意义。此外,仔细研究在 SC 和神经胶质瘤之间表达不同的 15 个 miRNA,特别是其中 5 个非 SC 特异性 miRNA,可能会增强我们对神经胶质瘤发生的理解。