Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukaemia
Date
2017
Authors
Narayan, N.
Morenos, L.
Phipson, B.
Willis, S.
Brumatti, G.
Eggers, S.
Lalaoui, N.
Brown, L.
Kosasih, H.
Bartolo, R.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Leukemia, 2017; 31(4):808-820
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
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© 2016, Springer Nature