TRIM47 overexpression is a poor prognostic factor and contributes to carcinogenesis in non-small cell lung carcinoma

Oncotarget. 2017 Apr 4;8(14):22730-22740. doi: 10.18632/oncotarget.15188.

Abstract

Non-small cell lung carcinoma (NSCLC) is the most common malignancy with the highest morbidity and mortality. In this study, we found that tripartite motif containing 47 (TRIM47) expression level was higher in tumor tissues than in normal adjacent tissues. Overexpression of TRIM47 closely correlated with poor prognosis in patients with NSCLC. Multivariate Cox regression analyses showed that TRIM47 overexpression could be considered an independent prognostic factor for NSCLC. TRIM47 depletion significantly inhibited cell proliferation and induced G1phase arrest in A549 and H358 cell lines. Moreover, TRIM47 silencing remarkably inhibited cell migration, cell invasion, and tumorigenicity in nude mice. Gene set enrichment analysis (GSEA) revealed that cancer-related process and pathways, including p53-cell cycle and NFκB-epithelial mesenchymal transition (EMT) pathway, were significantly correlated with TRIM47 expression. Real-time PCR and Western blot analysis revealed that TRIM47 exerts an inhibitory effect on p53 and an facilitatory effect on NF-κB, thereby promoting tumor proliferation and metastasis. Taken together, TRIM47 acts as a tumor oncogene in NSCLC. Our data provide insight into the possible biological mechanism of TRIM47 in the progression of NSCLC and highlight its usefulness as a potential therapeutic target.

Keywords: EMT; NSCLC; P53; TRIM47; cell cycle.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Carrier Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • TRIM47 protein, human