Abstract
BackgroundmicroRNAs (miRNAs) have been implicated in the control of many biological processes and their deregulation has been associated with many cancers. In recent years, the cancer stem cell (CSC) concept has been applied to many cancers including pediatric. We hypothesized that a common signature of deregulated miRNAs in the CSCs fraction may explain the disrupted signaling pathways in CSCs.Methodology/ResultsUsing a high throughput qPCR approach we identified 26 CSC associated differentially expressed miRNAs (DEmiRs). Using BCmicrO algorithm 865 potential CSC associated DEmiR targets were obtained. These potential targets were subjected to KEGG, Biocarta and Gene Ontology pathway and biological processes analysis. Four annotated pathways were enriched: cell cycle, cell proliferation, p53 and TGF-beta/BMP. Knocking down hsa-miR-21-5p, hsa-miR-181c-5p and hsa-miR-135b-5p using antisense oligonucleotides and small interfering RNA in cell lines led to the depletion of the CSC fraction and impairment of sphere formation (CSC surrogate assays).ConclusionOur findings indicated that CSC associated DEmiRs and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers.
Highlights
MicroRNAs are an abundant class of small (,22 nucleotides) non-coding single strand RNAs that regulate gene expression at a post-transcriptional level
Our findings indicated that cancer stem cell (CSC) associated differentially expressed miRNAs (DEmiRs) and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers
We propose that the defining features of CSCs can be described in terms of a coherent pattern of gene expression that is regulated by specific, aberrantly expressed miRNAs coordinated towards the maintenance and selfrenewal of cancer stem cells
Summary
MicroRNAs (miRNA) are an abundant class of small (,22 nucleotides) non-coding single strand RNAs (ncRNA) that regulate gene expression at a post-transcriptional level. These regulatory ncRNAs play important roles in the control of many biological processes and their deregulation has been implicated in a variety of pathological conditions, including many cancers. The regulation of self-renewal and the ability to generate progeny is based on common genes and mechanisms This subset of genes whose expression is deregulated by the miRNAs may explain the disrupted signaling pathways of the CSCs. microRNAs (miRNAs) have been implicated in the control of many biological processes and their deregulation has been associated with many cancers.
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