title: 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.
  
  
  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).
  
  
  CONCLUSIONS
  Our findings indicated that CSC associated DEmiRs and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers.
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Sanchez-Diaz
authors.forename: Tzu-Hung
authors.initials: TH
authors.lastname: Hsiao
authors.forename: Judy C
authors.initials: JC
authors.lastname: Chang
authors.forename: Dong
authors.initials: D
authors.lastname: Yue
authors.forename: Mimi C
authors.initials: MC
authors.lastname: Tan
authors.forename: Hung-I Harry
authors.initials: HI
authors.lastname: Chen
authors.forename: Gail E
authors.initials: GE
authors.lastname: Tomlinson
authors.forename: Yufei
authors.initials: Y
authors.lastname: Huang
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jaclyn Y
authors.initials: JY
authors.lastname: Hung
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53