Abnormal expression of histone demethylase Jumonji domain-containing protein 1A (JMJD1A) is associated with many kinds of cancers.JMJD1A is also a hypoxic response gene and its expression is regulated by hypoxia-inducible factor-1α (HIF-1α).In this study,we determined the role of J MJD1 A in development and hypoxia pathway.We also measured the expression of JMJD1A and two hypoxia factors glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) in 786-0 and HEK293 cells treated with different concentrations of NiCl2 (2.5-100 μM) for 24 h,and found that JMJD1A mRNA and protein were up-regulated with increased concentrations of NiCl2.We then observed that ascorbate could retard the up-regulated effect of NiCl2-induced JMJD1A expression in a dose-dependent manner through decreasing the stability of HIF-1α protein.lmmunohistochemical analysis further demonstrated ascorbate antagonized Ni2+-induced up-regulation of JMJD1A expression in 786-0,HEK293,and OS-RC-2 cells.These findings suggest that both Ni2+ and ascorbate can regulate the expression of histone demethylase JMJD1A,which is important for cancer development or inhibition.