MiR-181a/b and -c/d act as tumor suppressors in MLL-rearranged leukemia by targeting the MLL-complex

Mixed lineage leukemia (MLL) translocations are found in over 70% of infant leukemia. The wildtype MLL gene is involved in chromatin modification by methylating histone H3 (H3K4) and is crucial for leukemogenesis by interacting with the MLL-fusion proteins. MiR-181 was one of the first miRNAs described in the hematopoietic system and is repressed in MLL-rearranged AML. Here we show that forced expression of miR-181a/b and miR-181c/d bicistrons in MLL-rearranged leukemic cell lines decreased cell viability, cell growth, colony-formation and induced apoptosis. miR-181a/b and -c/d target the 3'UTR of the wildtype M…