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Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Short communication

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

Authors: Uri Rozovski, George A Calin, Tetsuro Setoyama, Lucilla D’Abundo, David M Harris, Ping Li, Zhiming Liu, Srdana Grgurevic, Alessandra Ferrajoli, Stefan Faderl, Jan A Burger, Susan O’Brien, William G Wierda, Michael J Keating, Zeev Estrov

Published in: Molecular Cancer | Issue 1/2013

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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.
Appendix
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Metadata
Title
Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
Authors
Uri Rozovski
George A Calin
Tetsuro Setoyama
Lucilla D’Abundo
David M Harris
Ping Li
Zhiming Liu
Srdana Grgurevic
Alessandra Ferrajoli
Stefan Faderl
Jan A Burger
Susan O’Brien
William G Wierda
Michael J Keating
Zeev Estrov
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-50

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