Knockdown of ZFAS1 suppresses the progression of acute myeloid leukemia by regulating microRNA-150/Sp1 and microRNA-150/Myb pathways.

Leukemia is the most frequent malignancy in children with acute myeloid leukemia (AML) as the second commonest type. Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been widely reported as an oncogenic factor in multiple malignancies including AML. However, the roles and molecular mechanisms of ZFAS1 in the tumorigenesis of AML are poor defined till now. In the present study, RT-qPCR assay showed that ZFAS1 was highly expressed in bone marrow of acute leukemia patients and AML cell lines. Loss-of-function analyses revealed that ZFAS1 knockdown inhibited proliferation and promoted apoptosis in AML cells and curbed AML xenograft growth in vivo. Bioinformatics analysis and luciferase reporter assay unveiled that microRNA-150 (miR-150) could interact with ZFAS1, Myb 3' UTR and Sp1 3' UTR. Moreover, ZFAS1 acted as a molecular sponge of miR-150, giving rise to the downregulation of miR-150 level and upregulation of Myb and Sp1 levels. Moreover, miR-150 overexpression resulted in the reduction of AML cell proliferative ability and the increase of cell apoptotic rate. Additionally, the inhibition of miR-150 abrogated ZFAS1 loss-mediated anti-leukemia effects. In summary, our data demonstrated that ZFAS1 knockdown hampered AML progression by regulating miR-150/Myb and miR-150/Sp1 pathways, providing some potential biomarkers or targets for the diagnosis and treatment of leukemia.