**7. Expression profile for miRNAs in astrocytomas**

in mammals strengthening genetic regulation. At the same time, microRNAs are regulated by oncogenes, tumour-repressing genes, epigenetic mechanisms, genetic abnormalities and defects in the miRNA biogenesis machinery [15]. Each one of these mechanisms may contribute by themselves or, more likely, together, to alter the expression of miRNAs in cancer

The central nervous system of mammals is controlled importantly by genetic regulation mechanisms. MicroRNAs contribute to this regulation; approximately 70% of identified miR-NAs until now are expressed in the brain and some of them are specific to the brain [17]. In recent studies, the pattern of expression for microRNAs was determined and it was shown

A wide variety of microRNAs are in neuronal subtypes with the highest concentration in the brain cortex and cerebellum [19, 20]. In the central nervous system, there are a large number of genes which originate miRNAs and their expression is different depending on the anatomical region. Specific microRNAs for the brain are miR-9, mir-124, miR-125, miR-128 and miR-129 [21–25]. MiR-124 and miR-128 are expressed mainly in neurons, whereas miR-23, miR-26 and miR-29 can be found enriched in astrocytes [10, 26, 27]. In the same way, the expression profile of miRNAs in the development and differentiation of the nervous system in mammals is fundamental, since changes have been documented in their expression when embryo stem cells develop neurogenesis and gliogenesis, which suggests that they may have an important role in differentiation or determination of the cell lineage

Calin et al. were the first ones to find evidence regarding the relation between miRNAs and cancer, demonstrating that miR-15 and miR-16 are located in a mutated region, in over half of chronic lymphocytic leukaemias in B-cells [30]. Several following studies have demonstrated that the expression profiles of several miRNAs are altered in different types of tumours such as glioblastoma, pituitary adenoma, prostate cancer, breast carcinoma, hepatocellular carcinoma, lung carcinoma, colorectal carcinoma, ovarian carcinoma, thyroid and cervical carcinoma, lymphoma and chronic lymphocytic leukaemia [31–35]. For this reason, some of them are considered tumour-suppressive genes or oncogenes [36–38]. Genetic events guiding the development of tumours in the brain are yet unknown; nevertheless, there is evidence which suggests that gliomas may surge starting from a subpopulation of cells within the tumoural mass; these cells have been called 'stem tumour cells', which maintain their ability for renewal and multi-potentiality. MiRNAs are important regulators of the process of differentiation and

that they regulate both development and functionality of the nervous system [9, 18].

**5. Patterns of expression for miRNAs in the brain**

62 Glioma - Contemporary Diagnostic and Therapeutic Approaches

**6. MicroRNAs and their relationship with cancer**

proliferation of stem cells (**Figure 4**) [39–41].

[15, 16].

[9, 14, 22, 28, 29].

Different expression patterns in miRNAs have been described in low- and high-grade astrocytomas including pilocytic, diffuse, anaplastic astrocytomas, and multi-form glioblastoma in adults. In these tumours, miRNAs participate in the cell proliferation, invasion, angiogenesis and differentiation [42, 43]. The first reports are very recent and started with the identification of miRNAs in the GBM in 2005. In this type of tumour, an overexpression of miR-221 was described and proposed as a possible specific marker, whereas miR-128, miR-181a, mir181b and miR-181c were found to be low expression, which probably reflects a loss of expression associated to the lack of differentiation in tumour cells [38]. In that same year, an over-expression of miR-21 in GBM and cell lines was described, comparing it with normal tissue. These effects were related with a reduction of apoptosis and malignant phenotype. On the contrary, the low expression of miR-21 promoted the activation of caspases and apoptosis [44]. Afterwards, in another study, miR-124 and miR-137 were identified, related with the neuronal differentiation in mouse stem cells, derived from a mouse oligodendroglioma and derived of human GBM. Besides, in a cell line of GBM, arrest in the cell cycle after transfecting miR-124 and miR-137 could be observed, which suggests that miR-124 and miR-137 may be target molecules for therapeutic treatments of this illness [44]. These studies suggest that miRNAs participate in multiple biological processes which are characteristic of GBM such as cell differentiation, proliferation, invasion, apoptosis and angiogenesis. Given that miRNAs may promote or limit the development of the tumour, they may be considered as having oncogenic potential or tumour-suppressive activities. MiRNAs analysed in this study and which are considered in the study as having oncogenic potential are miR-15b, miR-21 and miR-221 and the tumour suppressors are miR-124, miR-128, miR-137 and miR-221. Next, each one of them is described [5, 23, 45–48].
