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The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML
BACKGROUND: CCAAT/enhancer-binding protein-α (CEBPA) is crucial for normal granulopoiesis and is frequently disrupted in acute myeloid leukaemia (AML). Increasing evidence suggests that CEBPA exerts its effects, in parts, by regulating specific microRNAs (miRNAs), as previously shown for miR-223. Th...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906742/ https://www.ncbi.nlm.nih.gov/pubmed/20628397 http://dx.doi.org/10.1038/sj.bjc.6605751 |
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author | Eyholzer, M Schmid, S Wilkens, L Mueller, B U Pabst, T |
author_facet | Eyholzer, M Schmid, S Wilkens, L Mueller, B U Pabst, T |
author_sort | Eyholzer, M |
collection | PubMed |
description | BACKGROUND: CCAAT/enhancer-binding protein-α (CEBPA) is crucial for normal granulopoiesis and is frequently disrupted in acute myeloid leukaemia (AML). Increasing evidence suggests that CEBPA exerts its effects, in parts, by regulating specific microRNAs (miRNAs), as previously shown for miR-223. The aim of this study was to investigate the genome-wide pattern of miRNAs regulated by CEBPA in myeloid cells. METHODS: In Kasumi-1 cells, conditionally expressing CEBPA, we assessed the expression of 470 human miRNAs by microarray analysis. We further investigated the microarray results by qRT-PCR, luciferase reporter assays, and chromatin immunoprecipitation assays. RESULTS: In all, 18 miRNAs were more than two-fold suppressed or induced after CEBPA restoration. Among these 18 miRNAs, we focused on CEBPA-mediated regulation of the tumour-suppressive miR-29b. We observed that miR-29b is suppressed in AML patients with impaired CEBPA function or loss of chromosome 7q. We found that CEBPA selectively regulates miR-29b expression on its miR-29a/b1 locus on chromosome 7q32.3, whereas miR-29b2/c on chromosome 1q32.2 is not affected. CONCLUSION: This study reports the activation of the tumour-suppressive miR-29b by the haematopoietic key transcription factor CEBPA. Our data provide a rationale for miR-29b suppression in AML patients with loss of chromosome 7q or CEBPA deficiency. |
format | Text |
id | pubmed-2906742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-29067422011-07-13 The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML Eyholzer, M Schmid, S Wilkens, L Mueller, B U Pabst, T Br J Cancer Genetics and Genomics BACKGROUND: CCAAT/enhancer-binding protein-α (CEBPA) is crucial for normal granulopoiesis and is frequently disrupted in acute myeloid leukaemia (AML). Increasing evidence suggests that CEBPA exerts its effects, in parts, by regulating specific microRNAs (miRNAs), as previously shown for miR-223. The aim of this study was to investigate the genome-wide pattern of miRNAs regulated by CEBPA in myeloid cells. METHODS: In Kasumi-1 cells, conditionally expressing CEBPA, we assessed the expression of 470 human miRNAs by microarray analysis. We further investigated the microarray results by qRT-PCR, luciferase reporter assays, and chromatin immunoprecipitation assays. RESULTS: In all, 18 miRNAs were more than two-fold suppressed or induced after CEBPA restoration. Among these 18 miRNAs, we focused on CEBPA-mediated regulation of the tumour-suppressive miR-29b. We observed that miR-29b is suppressed in AML patients with impaired CEBPA function or loss of chromosome 7q. We found that CEBPA selectively regulates miR-29b expression on its miR-29a/b1 locus on chromosome 7q32.3, whereas miR-29b2/c on chromosome 1q32.2 is not affected. CONCLUSION: This study reports the activation of the tumour-suppressive miR-29b by the haematopoietic key transcription factor CEBPA. Our data provide a rationale for miR-29b suppression in AML patients with loss of chromosome 7q or CEBPA deficiency. Nature Publishing Group 2010-07-13 2010-07-13 /pmc/articles/PMC2906742/ /pubmed/20628397 http://dx.doi.org/10.1038/sj.bjc.6605751 Text en Copyright © 2010 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Genetics and Genomics Eyholzer, M Schmid, S Wilkens, L Mueller, B U Pabst, T The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML |
title | The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML |
title_full | The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML |
title_fullStr | The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML |
title_full_unstemmed | The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML |
title_short | The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML |
title_sort | tumour-suppressive mir-29a/b1 cluster is regulated by cebpa and blocked in human aml |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906742/ https://www.ncbi.nlm.nih.gov/pubmed/20628397 http://dx.doi.org/10.1038/sj.bjc.6605751 |
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