To determine the impact of SPOP, VDR and SETD7 on differentiation and stemness in colon cancer cell, we first tested the overexpression effects of these genes and found that SPOP and SETD7 positively regulated the expression of goblet cell differentiation marker HATH1, whereas VDR promoted the expression of columnar epithelial cell marker lactase in HCT116 cells (Fig. S5A,B). Here, VDR is linked to colonic neoplasm.