microRNA-7 modulates Rb1 and c-Myc expression in myeloid leukemias harboring c-Kit mutations. Mus musculus

The receptor tyrosine kinase, c-kit, plays a pivotal role in hematopoiesis and self-renewal. Aberrant activation of c-kit can be induced by genetic alterations and is thought to confer therapeutic resistance in leukemia. Significantly, the c-kit D816V mutation is a well-known indicator of poor prognosis in acute myeloid leukemias harboring t(8;21) chromosomal translocations; however, the mechanism by which this mutation promotes therapeutic resistance is still unclear. Our study identified that miR-7 directly targets Retinoblastoma-like Protein 1 (Rb1) and is regulated by the MEK pathway. In addition, we also found that c-Myc is upregulated by the D816V mutation, and is indirectly downregulated by miR-7. Overall design: Sample: (1)Ba/F3 (2)Ba/F3 c-kit V814 (3)MEK inhibitor treated Ba/F3 c-kit V814 ((1)vs(2)), ((2)vs(3)) To screen candidate microRNAs, an array was used to identify differences in microRNA expression between Ba/F3 cells and V814+Ba/F3 cells, as well as V814+Ba/F3 cells in the presence or absence of MEK inhibitor.