Author/Authors :
Jiang، نويسنده , , Xi and Huang، نويسنده , , Hao and Li، نويسنده , , Zejuan and Li، نويسنده , , Yuanyuan and Wang، نويسنده , , Xiao and Gurbuxani، نويسنده , , Sandeep and Chen، نويسنده , , Ping and He، نويسنده , , Chunjiang and You، نويسنده , , Dewen and Zhang، نويسنده , , Shuodan and Wang، نويسنده , , Jinhua and Arnovitz، نويسنده , , Stephen and Elkahloun، نويسنده , , Abdel and Price، نويسنده , , Colles and Hong، نويسنده , , Gia-Ming and Ren، نويسنده , , Haomin and Kunjamma، نويسنده , , Rejani B. and Neilly، نويسنده , , Mary Beth and Matthews، نويسنده , , Jonathan M. and Xu، نويسنده , , Mengyi and Larson، نويسنده , , Richard A. and Le Beau، نويسنده , , Michelle M. and Slany، نويسنده , , Robert A. and Liu، نويسنده , , Paul P. and Lu، نويسنده , , Jun and Zhang، نويسنده , , Jiwang and He، نويسنده , , Chuan and Chen، نويسنده , , Jianjun، نويسنده ,
Abstract :
Summary
sion 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.
