**3. Biogenesis**

**Figure 1.** Biogenesis and functions of miRNA. MicroRNA is transcribed by an RNA polymerase II or III so as to generate a transcript of primary RNA within the nucleus. The stem-handle structure of pri-miRNA is recognised and cut by a complex microprocessor composed by Drosha and DGCR8 to produce a precursor microRNA of 60–70 nucleotides in length. Pre-miRNA is then exported to the cytoplasm through the nuclear pores, by means of exportin-5, and it is then processed in the cytoplasm by Dicer-TRBP. The RNA double-chain molecule is separated by a helicase of RNA. One of the strands of the miRNA/miRNA\* duplex (the guiding strand or antisense strand) is incorporated, preferentially, in RISC, and it shall guide the miR-RISC complex towards the messenger RNA which shelters a complementary sequence to the miRNA. Once the RNAm is recognised, RISC may regulate the translation by inhibiting the starter or lengthening

The most frequent ones were astrocytoma (32%), medulloblastoma (19%), craniopharyngioma (11%) and ependymoma (10%). In fifth place, there are germimoma (with 4%). Mixed glioma,

Tumour damage cause into the displacement of encephalic structures, oedema, tissue damage and the symptomatology are according to location, size and time of evolution in the tumour. Cephalea was the most frequent symptom in our hospital, followed by irritability, vomit and papilloedema. The growth of cephalic perimeter is of prognostic value in children less than

Throughout the years, different classifications were postponed and applied for its study, based on histogenesis. Currently, the WHO has published its most recent classification [2] based on morphology and molecular changes. The reduction of costs and the increased ease of access to technology have made several medical centres approach this new era of molecular

Particularly in the case of astrocytoma, the most frequent tumours in the central nervous system of children, there are several considerations. The diffuse astrocytoma group themselves

primitive neuroectodermal tumours and ependymoblastomas made up 1–3% [1].

58 Glioma - Contemporary Diagnostic and Therapeutic Approaches

2 years of age [1].

pathology research [2].

steps. In some cases, the miR-RISC complex may return to the nucleus [8].

MiRNAs are initially transcribed as a long transcript known as primary miRNA (pri-miRNA) whose length goes between 3 and 4 kb, although some molecules may measure up to 10 kb. Pri-miRNAs are recognised in the nucleus by the complex composed by enzyme RNAse III

non-translated (3′UTR) (60%), in codifying sequences (25%), in introns, in non-codifying RNA sequences and in 5′UTR. The degree of complementarity between microRNA and RNAm determines the silencing mechanism. When complementarity is 100%, targeted RNAm is downgraded, which mostly happens with plants. In animals, complementarity is 100% in the seed region, but not throughout the microRNA in such a way that a mechanism of inhibition

Astrocytomas and miRNAs: Are They Useful? http://dx.doi.org/10.5772/intechopen.77419 61

The effector complex headed by the Argonaut protein probably interacts with translational systems to inhibit the synthesis of proteins at the beginning or in the elongation step, depending, probably, on the nature of the miRNA and the target transcript [13, 14]. Most microRNAs described in the human body exert their inhibiting effect in the cytoplasm; nevertheless, there exist some microRNAs as miR-29b which has a terminal sequence of hexanucleotides which allows it to return to the nucleus where it possibly undertakes its

The complexes formed by the microRNA/RISC-RNAm do not remain indefinitely in the cytoplasm, but they are rather transported towards structures of cytoplasmic processing, called P-bodies, where the downgrading of RNAm may take place due to deadenylation and decapping, or it is also stored and then separated from the repression complex and the P-body and

MicroRNAs participate in fundamental cell processes such as determining the cell lineage, apoptosis, proliferation, migration and regulation of the cell cycle, in which the translation of specific genes is highly precise and coordinated. MicroRNAs make up complex regulatory networks with its target genes, representing common mechanisms that have evolved

**Figure 3.** Model which shows the effects of deregulation of miRNAs in the development of the glioma. Under normal physiological conditions, the expression of miRNAs is important for the induction of differentiation in the SNC and abrogation of the self-renewal of the stem cell. The loss of expression of miRNAs results in the creation of pre-malignant stem cells, which are hyperproliferative and non-differentiated, which may progress into a glioma of low to high grade.

of the target messenger takes place.

returns to the translational machinery (**Figure 3**).

Additional oncogenic mutations may facilitate the malignant phenotype.

functions.

**Figure 2.** Biogenesis of the microRNA within the nucleus (a–c), maturing of the cytoplasm (d), formation of the microRNA-RISC complex which, depending on the sequence, shall return to the nucleus (e) or shall join its target RNAm to inhibit the translation (f) and finally the microRNA/RISC-RNAm complexes are stored in p-bodies where they are degraded or they return to the translation (g).

Drosha and DGCR8 (protein with a binding domain to double-strand RNA). This complex cuts the structure in a fork, becoming now a precursor miRNA (pre-miRNA) with a length of 60–80 nucleotides. The pre-miRNA is recognisable because of exportin 5 (nuclear exporting factor) and the nuclear protein Ran-GTP. Both transport pre-miRNA towards the cytoplasm. The Dicer and TRBP enzymes (proteins with binding domain to RNA) undertake a second cut in the base of the stem-handle and they generate an RNA molecule, double strand, of 18–24 nucleotides in size [12]. A great protein complex known as silencing complex induced by RNA (RISC) is associated with duplex RNA and separates both chains. RISC is a tetrameric complex made up of Dicer, TRBP (protein with binding domain to RNA), PACT (Activating Protein) and Ago2 (Protein of the Argonaut family). Ago2 identifies the target RNAm based on the complementarity with the associated single-strand microRNA. Recognised sequences of target RNAm are located mainly in region 3, non-translated (3′UTR). Generally speaking, only one strand is incorporated within RISC and the other one is downgraded. This miRNA guides RISC towards the target messenger inhibiting its translation (**Figure 2**) [13, 14].
