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

Biomed Pharmacother. 2018 Oct:106:890-895. doi: 10.1016/j.biopha.2018.06.173. Epub 2018 Jul 12.

Abstract

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.

Keywords: EZH2; HOXD-AS1; Osteosarcoma; lncRNA; p57.

MeSH terms

  • Animals
  • Binding Sites
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p57 / metabolism
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Epigenesis, Genetic*
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction
  • Time Factors
  • Tumor Burden
  • Young Adult

Substances

  • CDKN1C protein, human
  • Cyclin-Dependent Kinase Inhibitor p57
  • RNA, Long Noncoding
  • long non-coding RNA HOXD-AS1, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein