TRIM23 overexpression is a poor prognostic factor and contributes to carcinogenesis in colorectal cancer

J Cell Mol Med. 2020 May;24(10):5491-5500. doi: 10.1111/jcmm.15203. Epub 2020 Mar 30.

Abstract

The tripartite motif (TRIM) family proteins play a great role in carcinogenesis. However, the expression pattern, prognostic value and biological functions of tripartite motif containing 23 (TRIM23) in colorectal cancer (CRC) are poorly understood. Here, we found that TRIM23 is up-regulated and associated with tumour size, lymph node metastasis, American Joint Committee on Cancer (AJCC) stage and poor prognosis in CRC. Multivariate Cox regression analyses revealed that TRIM23 overexpression could be identified as an independent prognostic factor for CRC. TRIM23 could promote the proliferation of CRC cell in vitro and in vivo; additionally, TRIM23 depletion induced G1-phase arrest. Gene set enrichment analysis (GSEA) revealed that P53 and cell cycle signalling pathway-related genes were enriched in patients with high TRIM23 expression levels. We show in this study that TRIM23 physically binds to P53 and enhances the ubiquitination of P53, thereby promoting tumour proliferation. Thus, our data indicated that TRIM23 acts as an oncogene in colorectal carcinogenesis and may provide a novel therapeutic target for CRC management.

Keywords: P53; TRIM23; cell cycle; colorectal cancer; proliferation.

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics*
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Expression*
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Signal Transduction
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • TRIM23 protein, human
  • Tumor Suppressor Protein p53
  • GTP-Binding Proteins