title: The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a class of small RNAs that have been linked to a number of diseases including cancer. The potential application of miRNAs in the diagnostics and therapeutics of ovarian and other cancers is an area of intense interest. A current challenge is the inability to accurately predict the functional consequences of exogenous modulations in the levels of potentially therapeutic miRNAs.
  
  
  METHODS
  In an initial effort to systematically address this issue, we conducted miRNA transfection experiments using two miRNAs (miR-7, miR-128). We monitored the consequent changes in global patterns of gene expression by microarray and quantitative (real-time) polymerase chain reaction. Network analysis of the expression data was used to predict the consequence of each transfection on cellular function and these predictions were experimentally tested.
  
  
  RESULTS
  While ~20% of the changes in expression patterns of hundreds to thousands of genes could be attributed to direct miRNA-mRNA interactions, the majority of the changes are indirect, involving the downstream consequences of miRNA-mediated changes in regulatory gene expression. The changes in gene expression induced by individual miRNAs are functionally coordinated but distinct between the two miRNAs. MiR-7 transfection into ovarian cancer cells induces changes in cell adhesion and other developmental networks previously associated with epithelial-mesenchymal transitions (EMT) and other processes linked with metastasis. In contrast, miR-128 transfection induces changes in cell cycle control and other processes commonly linked with cellular replication.
  
  
  CONCLUSIONS
  The functionally coordinated patterns of gene expression displayed by different families of miRNAs have the potential to provide clinicians with a strategy to treat cancers from a systems rather than a single gene perspective.
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, 30332, USA.
authors.forename: Shubin W
authors.initials: SW
authors.lastname: Shahab
authors.forename: Lilya V
authors.initials: LV
authors.lastname: Matyunina
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Hill
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
authors.forename: L DeEtte
authors.initials: LD
authors.lastname: Walker
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D066246:ErbB Receptors; D035683:MicroRNAs; C545189:MIRN128 microRNA, human; C549242:MIRN7-1 microRNA, human; C512478:EGFR protein, human