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

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autor(en): 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
Zeitschrift: Cancer Cell
Jahr der Veröffentlichung: 2012
Band: 22
Heftnummer: 4
Seitenbereich: 524-535
ISSN: 1535-6108


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.



FAU-Autoren / FAU-Herausgeber

Slany, Robert Prof. Dr.
Lehrstuhl für Genetik


Autor(en) der externen Einrichtung(en)
Loyola University Chicago
National Human Genome Research Institute (NHGRI)
University of Chicago


Zitierweisen

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.

BibTeX: 

Zuletzt aktualisiert 2018-08-12 um 13:50