ESR1 and bone neoplasm: It promoted the apoptosis of human bone cancer in vitro and in vivo in nude mice that had undergone orthotopic tumor implants by modulating the expression levels of the apoptosis-related factors ERK, Akt [176], Bcl-2, Bax, and caspase-3 and decreasing the level of miR-375, an ER signaling-related miRNA, in ER-positive U2OS cells [175].