Fig. 7

Schematic illustrates the mechanism by which miR-143 directly binds to MSI2 and inhibits its efficacy in AML progression. MSI2/DLL1/Notch1 axis: MSI2 binds directly to DLL1 mRNA and stabilize it at the post-transcriptional level. Then DLL1 agonistic ligands trigger proteolytic cleavage of Notch1 receptors to generate the NICD. NICD/CSL-dependent transcriptional activation of target gene HES1 is upregulated by canonical Notch signaling cascades to maintain stemness of AML cells. MSI2/Snail1/MMPs axis: MSI2 stabilizes Snail1 mRNA and induced transcriptional upregulation of Snail1, which in turn activated both MMP2 and MMP9 to promote AML cell migration. AML, Acute myeloid leukemia; MiR-143, MicroRNA-143; MSI2, Musashi-2; DLL, delta-like canonical Notch ligand; NICD, Notch intracellular domain; MAML, mastermind like protein; CSL, cBF1-suppressor of hairless-LAG1; HES1, hes family bHLH transcription factor 1; Snail1: snail family transcriptional repressor 1; MMP matrix metalloproteinase