Abstract
MicroRNAs, also called miRNAs or simply miR-, represent a unique class of non-coding RNAs that have gained exponential interest during recent years because of their determinant involvement in regulating the expression of several genes. Despite the increasing number of mature miRNAs recognized in the human species, only a limited proportion is engaged in the ontogeny of the central nervous system (CNS). miRNAs also play a pivotal role during the transition of normal neural stem cells (NSCs) into tumor-forming NSCs. More specifically, extensive studies have identified some shared miRNAs between NSCs and neural cancer stem cells (CSCs), namely miR-7, -124, -125, -181 and miR-9, -10, -130. In the context of NSCs, miRNAs are intercalated from embryonic stages throughout the differentiation pathway in order to achieve mature neuronal lineages. Within CSCs, under a different cellular context, miRNAs perform tumor suppressive or oncogenic functions that govern the homeostasis of brain tumors. This review will draw attention to the most characterizing studies dealing with miRNAs engaged in neurogenesis and in the tumoral neural stem cell context, offering the reader insight into the power of next generation miRNA-targeted therapies against brain malignances.
Highlights
From the beginning of the new millennium, biomedical research on microRNAs has gained significant attention as cardinal elements in regulatory gene machinery
According to the most recent miRNA database, almost 2700 mature miRNAs have been annotated in the human species with some of them highly expressed in brain transcriptomes [1]. miRNA biogenesis takes place via RNA polymerase II or III in the shape of a primary transcript called pri-miRNA, that is further processed in the nuclear compartment into a pre-miRNA by the ribonuclease Drosha, with the cofactor binding protein DGCR8 Microprocessor Complex Subunit (DGCR8)
The pre-miRNA recognition by the specific exportin 5 is responsible for the cytoplasmic translocation where the complex Dicer1, Ribonuclease III/TAR RNA binding protein (Dicer/TRBP) gives rise to a 21–22 nucleotide duplex that, eventually loaded via the Argonaute protein, is integrated as mature miRNA into the RNA induced silencing complex (RISC). miRNAs mostly impair target mRNAs or abolish their translation by binding to complementary sequences in the 3’ untranslated region (3’UTR) [2]
Summary
From the beginning of the new millennium, biomedical research on microRNAs ( known as miRNA or miR-) has gained significant attention as cardinal elements in regulatory gene machinery. A recent study [47] dealing with the miR-302 cluster, which encodes for miR-302a/b/c/d and miR-367, was able to identify a set of 146 high-confidence targets corresponding to a wide range of functional categories such as cell proliferation homeostasis, chromatin organization, vesicle transport, actin cytoskeleton and extracellular matrix constituents These heterogeneous properties are under the control of the overall inhibition of neural differentiation (high content of miR-302) and affect trophectodermal fate, which besides the recognized regulation of TGFβ, puts into action BMP signaling. Jönsson and collaborators [48], by miRNA array analysis, examined human fetal samples encompassing both hNPCs and floor-plate cells of a forebrain (FB), midbrain (MB) and hindbrain (HB) They found that miR-10 was constitutively and massively expressed in the HB and spinal cord (SC) and they succeeded in isolating 89 high-confidence miR-10 target genes, enriched for functions in transcription, actin cytoskeleton and ephrin receptor signaling. It is our aim that the reader gains insight into the power of generation miRNA-targeted therapies against human brain tumors
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