@article{c195dc6e8a044518adfde92fa201274e,
title = "Blockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia",
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.",
author = "Xi Jiang and Hao Huang and Zejuan Li and Yuanyuan Li and Xiao Wang and Sandeep Gurbuxani and Ping Chen and Chunjiang He and Dewen You and Shuodan Zhang and Jinhua Wang and Stephen Arnovitz and Abdel Elkahloun and Colles Price and Hong, {Gia Ming} and Haomin Ren and Kunjamma, {Rejani B.} and Neilly, {Mary Beth} and Matthews, {Jonathan M.} and Mengyi Xu and Larson, {Richard A.} and {Le Beau}, {Michelle M.} and Slany, {Robert K.} and Liu, {Paul P.} and Jun Lu and Jiwang Zhang and Chuan He and Jianjun Chen",
note = "Funding Information: The authors thank Dr. Janet D. Rowley for her support and constructive suggestions/comments and Dr. Peter Breslin for critical reading and constructive comments. We are also grateful to Drs. Gregory Hannon, Scott Hammond, Lin He, Scott Armstrong, and Michael Thirman for providing retroviral constructs. This work was supported in part by the National Institutes of Health (NIH) R01 Grant CA127277 (J.C.), American Cancer Society (ACS) Research Scholar grant (J.C.), The University of Chicago Committee on Cancer Biology (CCB) Fellowship Program (X.J.), LLS Special Fellowship (Z.L.), Gabrielle{\textquoteright}s Angel Foundation for Cancer Research (J.C., Z.L., and H.H.), Leukemia & Lymphoma Society (LLS) Translational Research Grant (J.D.R. and J.C.), the Fidelity Foundation (J.D.R. and J.C.), R01 HL95896 (J.Z.), and the Intramural Research Program of the National Human Genome Research Institute, NIH (A.E. and P.P.L.), NIH P01 CA40046 (M.M.L.B), and P30 CA014599 (CCSG) (M.M.L.B). ",
year = "2012",
month = oct,
day = "16",
doi = "10.1016/j.ccr.2012.08.028",
language = "English (US)",
volume = "22",
pages = "524--535",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}