Aberrantly expressed microRNAs and their implications in childhood central nervous system tumors Julia Alejandra Pezuk 1 & Karina Bezerra Salomão 2 & Mirella Baroni 2 & Carolina Alves Pereira 2 & Lenisa Geron 2 & María Sol Brassesco 3 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Even though the treatment of childhood cancer has evolved significantly in recent decades, aggressive central nervous system (CNS) tumors are still a leading cause of morbidity and mortality in this population. Consequently, the identification of molecular targets that can be incorporated into diagnostic practice, effectively predict prognosis, follow treatment response, and materialize into potential targeted therapeutic approaches are still warranted. Since the first evidence of the participation of miRNAs in cancer development and progression 20 years ago, notable progress has been made in the basic understanding of the contribution of their dysregulation as epigenetic driver of tumorigenesis. Nevertheless, among the plethora of articles in the literature, microRNA profiling of pediatric tumors are scarce. This article gives an overview of the recent advances in the diagnostic/prognostic potential of miRNAs in a selection of pediatric CNS tumors: medulloblastoma, ependymoma, pilocytic astrocytoma, glioblas- toma, diffuse intrinsic pontine glioma, atypical teratoid/rhabdoid tumors, and choroid plexus tumors. Keywords miRNA . Cancer . Children . Central nervous system . Review 1 MicroRNA biogenesis, function, and in cancer MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in regulating gene expression. MiRNAs were first described in 1993 in Caenorhabditis elegans as a tempo- ral control that regulated protein levels and allowed the devel- opment of the nematode [1]. Soon after that, miRNAs were observed in vertebrates and invertebrates as conserved mole- cules approximately 22 nucleotides long and characterized as important post-transcriptional gene regulators that inhibit protein translation [2]. These molecules are involved in all critical biological processes with unique expression patterns defined for each cell type. Alterations of their expression is commonly associated with disease, and thus miRNAs can be used as biomarkers [3]. MiRNAs are encoded in intergenic or intronic regions, and their expression is usually regulated as any other gene [4]. Most of them are transcribed by RNA polymerase II in the nucleus, originating a primary transcript (named pri-miRNA). Then, pri-miRNAs are processed by a microprocessor com- plex containing a RNase III enzyme, called DROSHA, that leads to the formation of a miRNA precursors (pré-miRNA). Then, pré-miRNA are exported to the cytoplasm by Exportin- 5, where another RNAse III enzyme called Dicer catalysis the ends of the molecule bringing forth miRNA duplexes. Next, the miRNA duplexes are associated to a protein complex named RISC (RNA-induced silencing complex) where only one strand will be selected to play its function [3, 5, 6]. Alterations on each step of the process can be associated with gene expression dysregulation causing many types of patho- logical conditions [7]. Numerous studies have shown that miRNA are important players for cancer initiation and progression [8, 9]. Although specific miRNAs are fundamental for each cell and tumor type, each miRNA can act as oncomiR or tumor suppressor, * María Sol Brassesco solbrassesco@usp.br 1 Anhanguera University of São Paulo, UNIAN/SP, Av. Dr. Rudge Ramos, 1501 - Jardim Abc, São Bernardo do Campo, SP 09639-000, Brazil 2 Ribeirão Preto School of Medicine, University of São Paulo, Av. Dr. Rudge Ramos, 1501 - Jardim Abc, São Bernardo do Campo, SP 09639-000, Brazil 3 Departamento de Biologia, FFCLRP-USP, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900 - Vila Monte Alegre, Ribeirão Preto, SP 14040-900, Brazil https://doi.org/10.1007/s10555-019-09820-6 Cancer and Metastasis Reviews (2019) 38:813–828 Published online: 3 December 2019