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

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 constitutiv...

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Autores principales: Rozovski, Uri, Calin, George A, Setoyama, Tetsuro, D’Abundo, Lucilla, Harris, David M, Li, Ping, Liu, Zhiming, Grgurevic, Srdana, Ferrajoli, Alessandra, Faderl, Stefan, Burger, Jan A, O’Brien, Susan, Wierda, William G, Keating, Michael J, Estrov, Zeev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671957/
https://www.ncbi.nlm.nih.gov/pubmed/23725032
http://dx.doi.org/10.1186/1476-4598-12-50
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author Rozovski, Uri
Calin, George A
Setoyama, Tetsuro
D’Abundo, Lucilla
Harris, David M
Li, Ping
Liu, Zhiming
Grgurevic, Srdana
Ferrajoli, Alessandra
Faderl, Stefan
Burger, Jan A
O’Brien, Susan
Wierda, William G
Keating, Michael J
Estrov, Zeev
author_facet Rozovski, Uri
Calin, George A
Setoyama, Tetsuro
D’Abundo, Lucilla
Harris, David M
Li, Ping
Liu, Zhiming
Grgurevic, Srdana
Ferrajoli, Alessandra
Faderl, Stefan
Burger, Jan A
O’Brien, Susan
Wierda, William G
Keating, Michael J
Estrov, Zeev
author_sort Rozovski, Uri
collection PubMed
description 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.
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spelling pubmed-36719572013-06-05 Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells Rozovski, Uri Calin, George A Setoyama, Tetsuro D’Abundo, Lucilla Harris, David M Li, Ping Liu, Zhiming Grgurevic, Srdana Ferrajoli, Alessandra Faderl, Stefan Burger, Jan A O’Brien, Susan Wierda, William G Keating, Michael J Estrov, Zeev Mol Cancer Short Communication 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. BioMed Central 2013-06-01 /pmc/articles/PMC3671957/ /pubmed/23725032 http://dx.doi.org/10.1186/1476-4598-12-50 Text en Copyright © 2013 Rozovski et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Rozovski, Uri
Calin, George A
Setoyama, Tetsuro
D’Abundo, Lucilla
Harris, David M
Li, Ping
Liu, Zhiming
Grgurevic, Srdana
Ferrajoli, Alessandra
Faderl, Stefan
Burger, Jan A
O’Brien, Susan
Wierda, William G
Keating, Michael J
Estrov, Zeev
Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
title Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
title_full Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
title_fullStr Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
title_full_unstemmed Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
title_short Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
title_sort signal transducer and activator of transcription (stat)-3 regulates microrna gene expression in chronic lymphocytic leukemia cells
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671957/
https://www.ncbi.nlm.nih.gov/pubmed/23725032
http://dx.doi.org/10.1186/1476-4598-12-50
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