Direct Binding of miR-155 to FLT3 Regulates Key Cellular Functions in Acute Myeloid Leukemia
Truong, A.; Warsi, S.; Naqchi, O.; Al-Haidari, A.
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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.
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