FOXP4-AS1 participates in the development and progression of osteosarcoma by downregulating LATS1 via binding to LSD1 and EZH2

Biochem Biophys Res Commun. 2018 Aug 25;502(4):493-500. doi: 10.1016/j.bbrc.2018.05.198. Epub 2018 Jun 5.

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNA has been confirmed to participate in a variety of cancers. The purpose of this study was to explore the effect of FOXP4-AS1 on the development of osteosarcoma (OS) and its underlying mechanism. FOXP4-AS1 expressions in 60 OS tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). We confirmed that FOXP4-AS1 was overexpressed in OS tissues than that of paracancerous tissues. The disease-free survival and overall survival of OS patients were not correlated with age, gender and tumor location, but remarkably correlated with FOXP4-AS1 expression, tumor size and lung metastasis. For in vitro experiments, MG63 cells expressed a higher expression of FOXP4-AS1, whereas U2OS cells expressed a lower expression, which were selected for the following studies. Overexpressed FOXP4-AS1 led to enhanced proliferation, migration and invasion, shortened G0/G1 phase, as well as inhibited cell cycle. Knockdown of FOXP4-AS1 in MG63 cells obtained the opposite results. Furthermore, RIP assay indicated that FOXP4-AS1 could inhibit LATS1 expression by binding to LSD1 and EZH2, so as to participate in OS development. In conclusion, these results revealed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. Furthermore, FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1 via binding to LSD1 and EZH2.

Keywords: EZH2; FOXP4-AS1; LATS1; LSD1; Osteosarcoma.

MeSH terms

  • Adolescent
  • Adult
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Down-Regulation
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • Histone Demethylases / metabolism*
  • Humans
  • Male
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • PTEN Phosphohydrolase / genetics
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • Young Adult

Substances

  • FOXP4 antisense RNA 1, human
  • RNA, Long Noncoding
  • Histone Demethylases
  • KDM1A protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • LATS1 protein, human
  • Protein Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human