Liver X receptor α inhibits osteosarcoma cell proliferation through up-regulation of FoxO1

Cell Physiol Biochem. 2013;32(1):180-6. doi: 10.1159/000350134. Epub 2013 Jul 12.

Abstract

Background: Osteosarcoma is the most common primary bone malignancy of adolescents and young adults.

Methods: We analyzed liver X receptor α (LXRα) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent noncancerous tissues. Moreover, we investigated LXRα's potential role in regulating cell proliferation in Saos-2 and U2OS cells.

Results: We found that activation of LXRα, a member of nuclear receptor, was able to inhibit cell proliferation in Saos-2 and U2OS cells. At the molecular level, our results further revealed that expression of tumor suppressor gene, FoxO1, was up-regulated by LXRα activation. LXRα activates FoxO1 transcription through a direct binding on its promoter region.

Conclusion: LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Liver X Receptors
  • Orphan Nuclear Receptors / genetics
  • Orphan Nuclear Receptors / metabolism*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Transcription, Genetic
  • Up-Regulation

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Liver X Receptors
  • NR1H3 protein, human
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • RNA, Small Interfering
  • Cyclin-Dependent Kinase Inhibitor p27