title: Downregulation of miR-31, miR-155, and miR-564 in chronic myeloid leukemia cells.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. However, little is known about the role of miRNAs in chronic myeloid leukemia (CML). Our objective is to decipher a miRNA expression signature associated with CML and to determine potential target genes and signaling pathways affected by these signature miRNAs.
  
  
  RESULTS
  Using miRNA microarrays and miRNA real-time PCR we characterized the miRNAs expression profile of CML cell lines and patients in reference to non-CML cell lines and healthy blood. Of all miRNAs tested, miR-31, miR-155, and miR-564 were down-regulated in CML cells. Down-regulation of these miRNAs was dependent on BCR-ABL activity. We next analyzed predicted targets and affected pathways of the deregulated miRNAs. As expected, in K562 cells, the expression of several of these targets was inverted to that of the miRNA putatively regulating them. Reassuringly, the analysis identified CML as the main disease associated with these miRNAs. MAPK, ErbB, mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF) were the main molecular pathways related with these expression patterns. Utilizing Venn diagrams we found appreciable overlap between the CML-related miRNAs and the signaling pathways-related miRNAs.
  
  
  CONCLUSIONS
  The miRNAs identified in this study might offer a pivotal role in CML. Nevertheless, while these data point to a central disease, the precise molecular pathway/s targeted by these miRNAs is variable implying a high level of complexity of miRNA target selection and regulation. These deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of CML, and propose possible new avenues for therapeutic treatment.
authors.affiliation: Felsenstein Medical Research Center, Beilinson Hospital, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Oshrat Hershkovitz
authors.initials: OH
authors.lastname: Rokah
authors.forename: Galit
authors.initials: G
authors.lastname: Granot
authors.forename: Adelina
authors.initials: A
authors.lastname: Ovcharenko
authors.forename: Shira
authors.initials: S
authors.lastname: Modai
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology; D015536:Down-Regulation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; C534612:MIRN31 microRNA, human; C577008:MIRN564 microRNA, human; D035683:MicroRNAs