Tribbles Pseudokinase 2 Promotes the Proliferation, Migration, and Invasion of Osteosarcoma through Modulating AP4/p21 Pathway

Ann Clin Lab Sci. 2022 May;52(3):406-415.

Abstract

Objective: At present, the efficacy of the clinical treatment of osteosarcoma is limited. We aimed to investigate the role of Tribbles pseudokinase 2 (TRIB2) in the progression of osteosarcoma and the underlying molecular mechanism.

Materials and methods: TRIB2 expression in osteosarcoma tissues and cells was measured via western blot analysis and quantitative reverse transcription polymerase chain reaction. Mouse xenograft tumor model was established to investigate the in vivo effect of Tribbles pseudokinase 2 on the development of osteosarcoma.

Results: We found that TRIB2 expression was increased in osteosarcoma tissues and cell lines compared with that in tumor adjacent normal tissues and normal bone cell line. Suppressing TRIB2 expression inhibited the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically, TRIB2 interacted with AP4, thereby inhibiting p21 expression at transcriptional level. In a mouse xenograft tumor model, TRIB2 overexpression promoted the growth of osteosarcoma by inhibiting p21 expression, which was reversed by AP4 silence.

Conclusion: Therefore, targeting TRIB2 may become a potential approach for osteosarcoma treatment.

Keywords: Mice; Osteosarcoma; Polymerase Chain Reaction; Tribbles Pseudokinase 2.

MeSH terms

  • Animals
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA-Binding Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins* / metabolism
  • Mice
  • Neoplasm Invasiveness / pathology
  • Osteosarcoma* / metabolism
  • Osteosarcoma* / pathology
  • RNA-Binding Proteins

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • REPIN1 protein, human
  • RNA-Binding Proteins
  • TRIB2 protein, human