Recent studies show that distal-less homeobox (DLX) 5 binds directly to the Notch1 promoter, which triggers upregulation of gene transcription in osteosarcoma cells, and that SIRT6 epigenetically regulates Notch1 transcription via DNA methyltransferase (DNMT) 1 in adipose-derived stem cells20,21. Here, NOTCH1 is linked to osteosarcoma.