Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells

Mol Cancer. 2013 Jun 1;12:50. doi: 10.1186/1476-4598-12-50.

Abstract

Backgrounds: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic
  • Protein Binding
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*

Substances

  • MicroRNAs
  • STAT3 Transcription Factor