Long noncoding RNA HOXD-AS1 aggravates osteosarcoma carcinogenesis through epigenetically inhibiting p57 via EZH2.

Osteosarcoma is the most common primary malignant bone tumor and long non-coding RNAs (lncRNAs) have been proved to epigenetically regulate the oncogenesis of osteosarcoma. In this research, we investigate the role of lncRNA HOXD-AS1 on the osteosarcoma oncogenesis. Results revealed that HOXD-AS1 expression level was significantly up-regulated in osteosarcoma tissue and cells, moreover, the aberrant overexpression predicted the poor prognosis of osteosarcoma patients. Loss-of-functional experiments indicated that HOXD-AS1 silencing inhibited the osteosarcoma cells proliferation and induced G1/G0 phase arrest in vitro, and repressed tumor cell growth in vivo. Mechanistic investigations showed that HOXD-AS1 epigenetically repressed p57 through recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p57. Rescue experiments revealed that p57 could recover the oncogenic role of HOXD-AS1 on osteosarcoma. In conclusion, our study confirmed that HOXD-AS1 could interact with EZH2, and then repress p57 expression, to aggravate osteosarcoma oncogenesis. which provide new idea for the osteosarcoma tumorigenesis.