title: Functional implications of microRNAs in acute myeloid leukemia by integrating microRNA and messenger RNA expression profiling.
abstract: BACKGROUND
  The expression of microRNAs (miRNAs) is deregulated in acute myeloid leukemia (AML), but the corresponding functional miRNA-controlled pathways are poorly understood. Integration of messenger RNA (mRNA) and miRNA expression profiling may allow the identification of functional links between the whole transcriptome and microRNome that are involved in myeloid leukemogenesis.
  
  
  METHODS
  We integrated miRNA and mRNA expression profiles obtained from 48 newly diagnosed AML patients by using 2 different microarray platforms and performed correlation, gene ontology, and network analysis. Experimental validation was also performed in AML cell lines using miRNA oligonucleotide mimics and functional assays.
  
  
  RESULTS
  Our analysis identified a strong positive correlation between HOX-related genes and miR-10 and miR-20a. Furthermore, we observed a negative correlation between miR-181a and miR-181b, miR-155, and miR-146 expression with that of genes involved in immunity and inflammation (eg, IRF7 and TLR4) and a positive correlation between miR-23a, miR-26a, miR-128a, and miR-145 expression with that of proapoptotic genes (eg, BIM and PTEN). These correlations were confirmed by gene ontology analyses, which revealed the enrichment of members of the homeobox, immunity and inflammation, and apoptosis biological processes. Furthermore, we validated experimentally the association of miR-145, miR-26a, and miR-128a with apoptosis in AML.
  
  
  CONCLUSIONS
  Our results indicate that by integrating the transcriptome and microRNome in AML cells, it is possible to identify previously unidentified putative functional miRNA-mRNA interactions in AML.
authors: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, USA.
authors: Violaine
authors: V
authors: Havelange
authors: Nicole
authors: N
authors: Stauffer
authors: Catherine C E
authors: CC
authors: Heaphy
authors: Stefano
authors: S
authors: Volinia
authors: Michael
authors: M
authors: Andreeff
authors: Guido
authors: G
authors: Marcucci
authors: Carlo M
authors: CM
authors: Croce
authors: Ramiro
authors: R
authors: Garzon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005629:Frozen Sections; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D005801:Genes, Homeobox / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; C545189:MIRN128 microRNA, human; C541010:MIRN145 microRNA, human; C528163:MIRN26 microRNA, human