Decitabine (DAC), a DNA methylation inhibitor can inhibit in vitro cell proliferation, mobility, anchoring independence, and spheroid formation, reduce in vivo xenograft tumor growth and metastasis and reduce the expression of tumor stem cell markers such as SOX2, OCT4, NANOG, and CRISPR/CAS9-mediated ESR1 gene knockout, effectively eliminating the abovementioned effects of DAC, and demonstrating that the inhibitory effect of DAC on osteosarcoma depends on the presence of the ESR1 gene [48]. This evidence concerns the gene ESR1 and osteosarcoma.