Blockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia

Jiang X, Huang H, Li Z, Li Y, Wang X, Gurbuxani S, Chen P, He C, You D, Zhang S, Wang J, Arnovitz S, Elkahloun A, Price C, Hong GM, Ren H, Kunjamma RB, Neilly MB, Matthews JM, Xu M, Larson RA, Le Beau MM, Slany R, Liu PP, Lu J, Zhang J, He C, Chen J (2012)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2012

Journal

Cancer Cell Elsevier (Cell Press)

Book Volume: 22

Pages Range: 524-535

Journal Issue: 4

DOI: 10.1016/j.ccr.2012.08.028

Abstract

Expression of microRNAs (miRNAs) is under stringent regulation at both transcriptional and posttranscriptional levels. Disturbance at either level could cause dysregulation of miRNAs. Here, we show that MLL fusion proteins negatively regulate production of miR-150, an miRNA widely repressed in acute leukemia, by blocking miR-150 precursors from being processed to mature miRNAs through MYC/LIN28 functional axis. Forced expression of miR-150 dramatically inhibited leukemic cell growth and delayed MLL-fusion-mediated leukemogenesis, likely through targeting FLT3 and MYB and thereby interfering with the HOXA9/MEIS1/FLT3/MYB signaling network, which in turn caused downregulation of MYC/LIN28. Collectively, we revealed a MLL-fusion/MYC/LIN28⊣miR-150⊣FLT3/MYB/HOXA9/MEIS1 signaling circuit underlying the pathogenesis of leukemia, where miR-150 functions as a pivotal gatekeeper and its repression is required for leukemogenesis. © 2012 Elsevier Inc.

Authors with CRIS profile

Robert Slany Lehrstuhl für Genetik

Involved external institutions

University of Chicago US United States (USA) (US) Loyola University Chicago US United States (USA) (US) Yale University US United States (USA) (US) National Human Genome Research Institute (NHGRI) US United States (USA) (US)

How to cite

APA:

Jiang, X., Huang, H., Li, Z., Li, Y., Wang, X., Gurbuxani, S.,... Chen, J. (2012). Blockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia. Cancer Cell, 22(4), 524-535. https://dx.doi.org/10.1016/j.ccr.2012.08.028

MLA:

Jiang, Xi, et al. "Blockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia." Cancer Cell 22.4 (2012): 524-535.

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