DDX11-AS1 contributes to osteosarcoma progression via stabilizing DDX11

Life Sci. 2020 Aug 1:254:117392. doi: 10.1016/j.lfs.2020.117392. Epub 2020 Jan 31.

Abstract

Increasing evidence has uncovered that long noncoding RNAs (lncRNAs) play extremely important roles in numerous steps of gene regulation concerning the progression of tumors. Defined as a kind of lncRNA, DDX11-AS1 has been considered to be closely related to the tumorigenesis of malignancies. Nevertheless, the underlying regulatory role of it in osteosarcoma remains to be analyzed and elucidated. In this research, a dramatically upregulated expression of DDX11-AS1 was detected in osteosarcoma cells. Loss-of-function assays revealed that decreased expression of DDX11-AS1 impaired osteosarcoma cell proliferation, metastasis as well as epithelial-mesenchymal transition (EMT) process. Afterwards, molecular mechanism tests validated that DDX11-AS1 could sponge miR-873-5p to upregulate DDX11 expression in osteosarcoma. Additionally, functional tests delineated that upregulation of miR-873-5p inhibited cell proliferation, metastasis as well as EMT process in osteosarcoma progression. Further, DDX11-AS1 was verified to regulate the mRNA stability of DDX11 through binding with IGF2BP2 in osteosarcoma. Final rescue tests in vitro and in vivo further elucidated that DDX11 overexpression could reversed the DDX11-AS1 downregulation-mediated effect on osteosarcoma progression. To sum up, DDX11-AS1 contributes to osteosarcoma progression via stabilizing DDX11.

Keywords: DDX11; DDX11-AS1; IGF2BP2; Osteosarcoma; miR-873-5p.

MeSH terms

  • Antisense Elements (Genetics)*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Protein Binding
  • RNA, Long Noncoding / genetics
  • RNA-Binding Proteins / metabolism
  • Up-Regulation

Substances

  • Antisense Elements (Genetics)
  • IGF2BP2 protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • DNA Helicases
  • DDX11 protein, human
  • DEAD-box RNA Helicases