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https://hdl.handle.net/2440/118197
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Type: | Journal article |
Title: | Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukaemia |
Author: | Narayan, N. Morenos, L. Phipson, B. Willis, S. Brumatti, G. Eggers, S. Lalaoui, N. Brown, L. Kosasih, H. Bartolo, R. Zhou, L. Catchpoole, D. Saffery, R. Oshlack, A. Goodall, G. Ekert, P. |
Citation: | Leukemia, 2017; 31(4):808-820 |
Publisher: | Springer Nature |
Issue Date: | 2017 |
ISSN: | 0887-6924 1476-5551 |
Statement of Responsibility: | N. Narayan, L. Morenos, B. Phipson, S. N. Willis, G. Brumatti, S. Eggers, N. Lalaoui, L. M. Brown, H. J. Kosasih, R. C. Bartolo, L. Zhou, D. Catchpoole, R. Saffery, A. Oshlack, G. J. Goodall and P. G. Ekert |
Abstract: | Enforced expression of microRNA-155 (miR-155) in myeloid cells has been shown to have both oncogenic or tumour-suppressor functions in acute myeloid leukaemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML data sets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favours selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease. Strikingly, we show that intermediate and high miR-155 expression also regulate very different subsets of miR-155 targets and have contrasting downstream effects on the transcriptional environments of AML cells, including genes involved in haematopoiesis and leukaemia. Furthermore, we show that elevated miR-155 expression detected in paediatric AML correlates with intermediate and not high miR-155 expression identified in our experimental models. These findings collectively describe a novel dose-dependent role for miR-155 in the regulation of AML, which may have important therapeutic implications.Leukemia advance online publication, 18 November 2016; doi:10.1038/leu.2016.279. |
Keywords: | Acute myeloid leukaemia; cancer genetics; cell biology; gene expression; miRNAs |
Rights: | © 2016, Springer Nature |
DOI: | 10.1038/leu.2016.279 |
Published version: | http://dx.doi.org/10.1038/leu.2016.279 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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