Overexpression of TRIM14 promotes tongue squamous cell carcinoma aggressiveness by activating the NF-κB signaling pathway

Oncotarget. 2016 Mar 1;7(9):9939-50. doi: 10.18632/oncotarget.6941.

Abstract

Tongue squamous cells carcinoma (TSCC) is one of the most lethal malignancies of oral cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that Tripartite motif containing 14(TRIM14) is markedly up-regulated in TSCC cell lines and clinical tissues. Immunohistochemical (IHC) analysis of 116 clinical TSCC specimens revealed that TRIM14 expression was significantly correlated with the TNM classification (T: P = 0.01; N: P < 0.001; M: P < 0.001) in patients with TSCC. Multivariate analysis indicated that TRIM14 expression might be an independent prognostic indicator for the survival of patients with TSCC. Ectopic expression of TRIM14 in TSCC cells promoted proliferation, angiogenesis, and increased resistance to cisplatin-induced apoptosis of TSCC cells in vitro. Furthermore, TRIM14 overexpressing significantly promoted the tumorigenicity of TSCC cells in vivo whereas silencing endogenous TRIM14 caused an opposite outcome. Moreover, we demonstrated that TRIM14 enhanced TSCC aggressiveness by activating NF-κB signaling. Together, our results provide new evidence that TRIM14 overexpression promotes the progression of TSCC and might represent a novel therapeutic target for its treatment.

Keywords: NF-κB pathway; TRIM14; TSCC; aggressiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Chick Embryo
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Multivariate Analysis
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / metabolism
  • Tripartite Motif Proteins
  • Xenograft Model Antitumor Assays

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • TRIM14 protein, human
  • Tripartite Motif Proteins