As shown in Figure 4C and 4D, p53 knockout dramatically reduced (even abolished) the upregulation effects of JMJD2D knockdown on the expression of p21 and PUMA protein and mRNA in liver cancer cells, indicating that JMJD2D knockdown-mediated upregulation of p21 and PUMA expression largely depends on p53. The gene discussed is KDM4D; the disease is liver cancer.