E2F1 and osteosarcoma: The tumor microenvironment may increase ANRIL. In fibroblast and osteosarcoma cell lines, ANRIL levels rise in response to a variety of DNA damaging agents via an ATM-induced E2F1 transcription-mediated pathway (29) and ANRIL contributes to pro-inflammatory cytokine expression by binding to YingYang-1 (YY1) in response to NFκB signaling (8).