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De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and development.


ABSTRACT:

Background

microRNAs (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/results

Using 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).

Conclusion

Our findings indicated that CSC associated DEmiRs and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers.

SUBMITTER: Sanchez-Diaz PC 

PROVIDER: S-EPMC3629228 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and development.

Sanchez-Diaz Patricia C PC   Hsiao Tzu-Hung TH   Chang Judy C JC   Yue Dong D   Tan Mimi C MC   Chen Hung-I Harry HI   Tomlinson Gail E GE   Huang Yufei Y   Chen Yidong Y   Hung Jaclyn Y JY  

PloS one 20130417 4


<h4>Background</h4>microRNAs (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.<h4>Methodology/results</h4>Using a high throughput qPCR approach we identified 26 CSC associ  ...[more]

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