TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway

Sci Rep. 2017 Feb 16:7:42411. doi: 10.1038/srep42411.

Abstract

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times. Functional studies demonstrated that overexpression of TRIM14 enhances osteosarcoma cell proliferation, clone formation, cell cycle procession, migration and invasion in vitro and promotes tumor growth in vivo, and conversely, its silencing has the opposite effects. Furthermore, TRIM14 overexpression induced activation of the AKT pathway. Inhibition of AKT expression reversed the TRIM14-mediated promotory effects on cell growth and mobility, in addition to TRIM14-induced epithelial-to-mesenchymal transition (EMT) and cyclin D1 upregulation. Our findings collectively suggest that TRIM14 functions as an oncogene by upregulating the AKT signaling pathway in osteosarcoma cells, supporting its potential utility as a therapeutic target for this disease.

MeSH terms

  • Adult
  • Animals
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • Tripartite Motif Proteins
  • Tumor Burden
  • Young Adult

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • TRIM14 protein, human
  • Tripartite Motif Proteins
  • Proto-Oncogene Proteins c-akt