## 3 miRNAs and Molecular Chaperones in Brain Tumors
### miRNAs in Brain Tumors  
MicroRNAs are short noncoding single stranded RNA (ssRNA) molecules, 19-25 nucleotides long, which regulate the expression of target genes post-transcriptionally by affecting either the stability or the translation of their mRNA [85]. The biogenesis of miRNAs consists of two highly regulated cleavage events [86]. The first one, occurring within the nucleus, generates a long hairpin-shaped RNA molecule called pre-miRNA [87; 88; 89; 90; 91; 92] which is exported to the cytoplasm, in which the second step occurs, producing a shorter double stranded RNA [93; 94; 95; 96; 97]. One of the strands, the star (*) strand or passenger strand, is degraded. The other strand (the guide strand or mature miRNA) forms the miRNA-induced silencing complex (miRRSC) that specifically recognizes a target mRNA, and downregulates gene expression by repression of translation or by mRNA cleavage [98; 99; 100; 101; 102; 103; 104]. However, in recent years it became clear that the passenger strand may not be degraded and could act as miRNA. Thus, according to a more recent nomenclature proposed by the miRBase registry, the two miRNA strands produced after the second cleavage are referred to as predominant product (indicated without *) and the strand from the opposite arm of the precursor  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Tumor** & **Cell of Origin** & **Molecular Features** & **Clinical Features** & **Ref. ** \\ \hline \multirow{4}{*}{Meningiomas} & & & Meningiomas are tumors of & \\  & & NF2 mutation & the meninges. Main & \\  & (WHO Grade I); & DAL1 loss & symptoms are headache, & \\  & & & PLEN mutation & seizures, psychotic-motor & \\  & & & 916 deletion & disabilities, mental & \\  & & & EGFR overexpression & \\  & & & & changes, visual disorders, & \\  & & & & language dysfunction. &  
(indicated with *). When the data are not sufficient to determine which sequence is predominant, the strands are indicated as 5p, i.e., present in the forward (5'-3') position, and 3p, i.e., located in the reverse (3'-5') position [105]. Since their discovery over 30 years ago in the nematode _Caenorhabditis elegans_[106; 107], a myriad of new miRNAs have been identified and annotated in the miRbase registry, and their number continuously increases thanks to the development of new high-throughput sequencing technologies and computational and bioinformatics prediction methods, which facilitate identification of miRNAs targets and their biological functions [108; 109; 110; 111; 112; 113; 114]. Currently, in humans over 2000 miRNAs have been annotated and validated, which regulate the vast majority of protein encoding genes, and thus most if not all biological events [115; 116; 117; 118; 119; 120; 121]. For this reason, any alteration of a miRNA normal expression profile was often related to pathology, including cancer as firstly suggested by the depletion or downregulation of miR-15a and miR-16a genes in the majority of B-cell chronic lymphocytic leukemia [122]. Typically, when miRNAs expression is amplified in cancer cells, they function as oncogenes and promote cancer development by negatively regulating tumor suppressor genes and/or genes that control cell differentiation or apoptosis. Conversely, when downregulated, miRNAs act as tumor suppressors and may inhibit tumorigenesis by regulating oncogenes and/or genes that control cell differentiation or apoptosis [123; 124]. There are several mechanisms inducing miRNAs dysregulation in cancer, such as (i) miRNAs genes amplification or deletion [122; 125]; (ii) abnormal transcriptional regulation of miRNA genes [126; 127]; (iii) epigenetic alterations, such as aberrant DNA methylation and histone acetylation of miRNAs genes, which, in turn, affect miRNAs levels [128; 129]; and (iv) defects in miRNAs biogenesis and maturation pathways, which can alter their expression [130; 131].