ZBED3 Functions as an Oncogene in Acute Myeloid Leukemia and Correlates with Poor Prognosis

Abstract

Background: Acute myeloid leukemia (AML) exhibits a high rate of relapse and chemotherapy resistance and is considered as an aggressive cancer with high mortality. Hence, it is urgent to identify new therapeutic targets to develop personalized medicine for patients with AML. Zinc finger BED-type containing 3 (ZBED3) shows high expression in various solid tumors, and this protein is linked with poor prognosis. However, the role of ZBED3 in AML is unclear. The aim of the present study was to assess the role of ZBED3 in AML. Methods: ZBED3 expression pattern in AML was assessed using several online databases and the correlation between ZBED3 expression and clinical outcomes in AML patients was analyzed. Lentiviruses silencing and overexpressing ZBED3 gene were respectively transfected in KG1a and K562 cells. The expression of ZBED3 was analyzed by quantitative real-time PCR and western blotting. The effects of ZBED3 knockdown or overexpression on the viability, apoptosis and cytosine arabinoside (Ara-C) resistance of leukemia cells were evaluated by the Cell Counting Kit-8 (CCK-8), colony formation assay and flow cytometry, respectively. The interaction between ZBED3 protein and Axin1 was examined by Co-immunoprecipitation experiment. Finally, the expression levels of the Wnt/β-catenin pathway-related proteins, including nuclear β-catenin, cyclin D1 and matrix metalloproteinase 7 (MMP7), were analyzed by western blotting. Results: ZBED3 was upregulated in AML, and its expression was enhanced in the relapsed cases of AML as compared to that in the newly diagnosed ones (p < 0.05). Moreover, a high ZBED3 expression level was associated with poor prognosis of AML patients. ZBED3 knockdown significantly suppressed the proliferation of leukemia cells and promoted apoptosis, whereas ZBED3 overexpression led to the opposite effects. ZBED3 overexpression also enhanced the resistance of leukemia cells to Ara-C. ZBED3 directly interacted with the Axin1 protein and regulated nuclear β-catenin, cyclin D1 and MMP7 protein levels in leukemia cells. Conclusions: Our study showed that high ZBED3 expression level contributes to the proliferation and chemoresistance of leukemia cells and correlates with poor outcomes in AML patients. ZBED3 may play an important role in leukemogenesis via the Wnt/β-catenin pathway.