**2. MicroRNA expression in glioblastoma**

Similar to other malignant tumors, GBM has the hallmarks of cancer: biological capabilities of sustaining proliferative signaling, inducing angiogenesis, evading growth suppressors, resistance to apoptosis, activating invasion and metastasis, genomic instability, reprogram‐ ming energy metabolism, limitless replicative potential, and evading immune destruction. It is generally accepted that hallmark features of GBM are not only a reflection of genetic abnormalities and aberrant signal transition but also the dysregulation of miRNA-mediated translational control. The miRNA-mRNA interactions transform the short "nonsense" sequences into endogenous oncogenes or tumor suppressors. miRNA expression patterns could define a tumor type, implying that certain changes in miRNAs might drive the malignant transformation to a particular tumor. Therefore, whether a miRNA acts as an oncomiR or tumor suppressor-miRNA depends on the regulated genes and cellular context.

The first report on altered miRNA expression in GBMs was published in 2005 (8). In this report, miR-21 was shown to be highly upregulated and to have antiapoptotic capabilities in GBM cells. These findings suggest that overexpressed miR-21 may function as an oncogene in GBMs by blocking expression of key apoptosis-enabling genes (8). In the same year, Ciafre et al. analyzed the global expression levels of 245 microRNAs in both GBM cell lines and patient biopsies (7). A systemic screen for miRNA aberrations by microarray identified a set of dysregulated miRNAs in GBM tissues, including the upregulation of miR-10b, miR-21, and miR-25 and downregulation of miR-128 and miR-181a/181b-/181c (7). Since then, miRNA expression in GBMs has been evaluated in several profiling studies. We previously reported that miR-10b, miR-21, miR-183, miR-92b, and miR-106b are highly expressed in GBMs compared with normal brain tissue, and miR-134, miR-302c, miR-324, miR-379, and miR-368-3p are downregulated in GBMs (9). In 2008, Silber et al. reported 13 miRNAs to be downregulated and three miRNAs to be upregulated in anaplastic astrocytomas and GBMs (11). Furthermore, they revealed that expression levels of miRNA-124 and miRNA-137 were significantly decreased compared with non-neoplastic brain tissue, and both of them induce differentiation of adult neural stem cells. Another study carried out by Godlewski et al. found 8 microRNAs to be upregulated and 11 downregulated when analyzing 245 microRNAs in the setting of GBM (12). A microarray-based study by Rao et al. analyzing 756 microRNAs identified another 55 upregulated and 29 downregulated microRNAs in primary and secon‐ dary GBMs and anaplastic astrocytoma compared with controls (13). This study not only validated the role of several deregulated microRNAs but also provided data for the develop‐ ment of a 23 microRNA signature pattern for distinguishing between anaplastic astrocytoma and GBM (13).
