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

Uri Rozovski1, George A Calin2, Tetsuro Setoyama2, Lucilla D’Abundo2, David M Harris1, Ping Li1, Zhiming Liu1, Srdana Grgurevic1, Alessandra Ferrajoli1, Stefan Faderl1, Jan A Burger1, Susan O’Brien1, William G Wierda1, Michael J Keating1 and Zeev Estrov1*

Author Affiliations

1 Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

2 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

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Molecular Cancer 2013, 12:50  doi:10.1186/1476-4598-12-50

Published: 1 June 2013

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.

Keywords:
CLL; microRNA; STAT3