Direct Binding of miR-155 to FLT3 Regulates Key Cellular Functions in Acute Myeloid Leukemia

Abstract Mutation in FLT3 protein is one of the most common mutations in acute myeloid leukemia (AML). Most patients with FLT3-ITD mutation detected at diagnosis or acquired during treatment display poor prognosis and resistance to tyrosine kinase inhibitors or chemotherapy. Existing clinical and pre-clinical data implicate miR-155 in the carcinogenesis of hematological cancers, including FLT3-assocaited AML. However, the role of miR-155 in regulating FLT3-ITD mutation remains elusive. In this study, we have applied loss-of-function studies using wild-type and mutated leukemic cell line models to validate the functional effect of miR-155 inhibition in leukemic cells. Our bioinformatics analysis indicates that FLT3 has a binding site for miR-155 which makes it a direct target of miR-155. Specific targeting of miR-155 by miR-155 inhibitor induced cell apoptosis and reduced FLT3-ITD-mediated cell proliferation and survival. Our data suggests that miR-155 could be a potential therapeutic target for FLT3-associated AML.