title: Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells.
abstract: BACKGROUND
  Approximately 1,000 microRNAs (miRs) are present in the human genome; however, little is known about the regulation of miR transcription. Because miR levels are deregulated in chronic lymphocytic leukemia (CLL) and signal transducer and activator of transcription (STAT)-3 is constitutively activated in CLL, we sought to determine whether STAT3 affects the transcription of miR genes in CLL cells.
  
  
  METHODS
  We used publically available data from the ENCODE project to identify putative STAT3 binding sites in the promoters of miR genes. Then we transfected CLL cells with STAT3-shRNA or with an empty vector, and to determine which miRs are differentially expressed, we used a miR microarray approach followed by validation of the microarray results for 6 miRs using quantitative real-time polymerase chain reaction (qRT-PCR).
  
  
  RESULTS
  We identified putative STAT3 binding sites in 160 promoter regions of 200 miRs, including miR-21, miR-29, and miR-155, whose levels have been reported to be upregulated in CLL. Levels of 72 miRs were downregulated (n = 63) or upregulated (n = 9). qRT-PCR confirmed the array data in 5 of 6 miRs.
  
  
  CONCLUSIONS
  The presence of activated STAT3 has a profound effect on miR expression in CLL cells.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Uri
authors.initials: U
authors.lastname: Rozovski
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Setoyama
authors.forename: Lucilla
authors.initials: L
authors.lastname: D'Abundo
authors.forename: David M
authors.initials: DM
authors.lastname: Harris
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Liu
authors.forename: Srdana
authors.initials: S
authors.lastname: Grgurevic
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Jan A
authors.initials: JA
authors.lastname: Burger
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; D050796:STAT3 Transcription Factor