Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics.

Abstract

Simple SummaryChildhood tumors of the central nervous system (CNS) constitute a grave disease and their diagnosis is difficult to be handled. To gain better knowledge of the tumor’s biology, it is essential to understand the underlying mechanisms of the disease. MicroRNAs (miRNAs) are small noncoding RNAs that are dysregulated in many types of CNS tumors and regulate their occurrence and development through specific signal pathways. However, different types of CNS tumors’ area are characterized by different deregulated miRNAs. Here, we hypothesized that CNS tumors could have commonly deregulated miRNAs, i.e., miRNAs that are simultaneously either upregulated or downregulated in all tumor types compared to the normal brain tissue, irrespectively of the tumor sub-type and/or diagnosis. The only criterion is that they are present in brain tumors. This approach could lead us to the discovery of miRNAs that could be used as pan-CNS tumoral therapeutic targets, if successful.Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.