Investigation of EPO-Mediated Rescue From P53-Dependent Apoptosis in DA3-EPOR Cells
Pham, Thuc-Nghi Duc
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The usage of recombinant human erythropoietin in clinics to treat cancer-associated anemia has shown unfortunate unforeseen tumour response to cytokine treatment. Although other cytokines have previously been shown to have an effect on p53-dependent tumourigenesis and apoptosis in vitro, the effects of erythropoietin on cancer development have only recently been observed in vivo, of which a potential mechanism has yet to be elucidated. To determine the potential mechanism by which erythropoietin mediates the evasion of apoptosis in cells, we used the wild-type p53-expressing murine leukemic cell line DA3-EPOR and induced apoptosis via daunorubicin and doxorubicin treatment. Our findings suggest that EPO rescues cells from p53-dependent apoptosis and enhances proteasomal degradation of p53 with a concomitant decrease in miR-34a, miR-34b/c, and lincRNA-p21 expression. EPO was also observed to increase p53 recruitment to the p21 promoter followed by increased p21 expression, suggesting an orchestrated shift from p53-dependent apoptosis to cell cycle arrest.