## 3 miRNAs and Molecular Chaperones in Brain Tumors  
Brain tumors are a heterogeneous group of neoplasms that differ in etiology, morphology, clinical manifestations, prognosis, and treatment. They were initially classified by the World Health Organization (WHO) according to their histologic features and presumed cellular origin. This type of characterization was the main tool used for many years in the diagnosis and management of patients, including decision on treatment strategy [33; 34; 35; 36] (Table 1). However, increasing genetic and epigenetic discoveries have shown that a classification only based on histopathological findings fell short of the mark. For this reason, in 2016, the WHO formulated an updated classification, which went beyond the old principle of diagnosis based only on microscopy and incorporated molecular parameters to define brain tumors entities. This new classification allows a more objective and accurate diagnosis, ensuring a more accurate assessment of prognosis and treatment response than the old one [37]. Brain tumors can be either benign (noncancerous), or malignant (cancerous). The latter can be distinguished into primary, arising directly within the brain, and secondary, namely metastatic brain tumors derived from other parts of the body that have metastasized to the brain [2; 38; 39; 40] (Table 1). Up to half of the metastatic brain tumors derive from lung cancer. Other types of tumors that commonly spread to the brain include melanoma, and breast, kidney, and colon cancer, although determining the site of the primary tumor is often difficult [38; 41; 42; 43; 44]. Genetic and environmental factors are implicated in the onset of primary brain tumors. The former are exemplified by neurofibromatosisis types 1 and 2, adenomatous polyposis syndrome, tuberous sclerosis, avoid basal cell carcinoma syndrome, [PERSON] syndrome, [PERSON] syndrome, and von Hippel-Lindau syndrome, whereas those linked to environmental factors are exemplified by those caused by ionizing radiation, and they are all considerably less frequent than secondary tumors (Table 1) [45; 46; 47; 48; 49; 50; 51] (Table 1). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Tumor** & **Cell of Origin** & **Molecular Features** & **Clinical Features** & **Ref.** \\ \hline Astrocytomas & & & \\ Diffuse astrocytoma (WHO Grade II); & & p16 deletion & \\ Anapalistic astrocytoma (WHO & p53 mutation & \\ Grade III); Pilocytic astrocytoma & Astrocyte & PTEN mutation & \\ (WHO Grade I); Glioblastoma & & EGFR amplification & Astrocytomas, \\ multiforme (WHO Grade IV); & & IDH1 mutation & oligodendrogliomas, \\ Gliosarcoma (WHO Grade IV) 1 & & & and ependimomas are \\ Oligodendrogliomas & & PEG3 deletion & gliomas that originate in the \\ Oligodendroglioma (WHO Grade II); & & EGFR amplification & glia and are extremely \\ -Anapalistic Oligodendroglioma; & & p53 mutation & invasive and malignant. \\ (WHO Grade III). & & p16 deletion & Main symptoms are \\ Ependymomas & & IDH1, IDH2 mutation & headache, seizures, nausea, \\ Ependymomas & & & vomiting, disturbed \\ Subependymoma (WHO Grade I); & & & vision, tingling \\ -Myxopapillary ependymoma (WHO & & & sensations, weakness, \\ Grade I); Ependymoma (WHO & & & difficult ambulation. \\ Grade II); Ependymoma, RELA & & & IGF1 upregulation \\ fusion-positive (WHO Grade II or III); & & & p16 deletion \\ Anapalistic ependymoma & & EGFR amplification & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Characteristics of the most common primary brain tumors. Current diagnostic approaches are based on imaging methods with subsequent histological examination of a biopsy. However, these approaches are limited by tumor localization and heterogeneity. Treatment choices can vary depending on tumor type and location, malignancy potential and patient's conditions, and include surgery, radiotherapy, chemotherapy, or a combination. Complete safe surgical resection, followed by radio/chemotherapy, represents the most common initial treatment for many primary brain tumors.