TRIM11, a direct target of miR-24-3p, promotes cell proliferation and inhibits apoptosis in colon cancer

Oncotarget. 2016 Dec 27;7(52):86755-86765. doi: 10.18632/oncotarget.13550.

Abstract

TRIM11 (tripartite motif-containing protein 11) is an E3 ubiquitin ligase recently identified as an oncogene in malignant glioma and lung cancer. In the present study, we report that expression of TRIM11 was increased in colon cancer (CC) tissue relative to paired normal tissues and that higher TRIM11 levels predicted poor overall survival (OS) and disease-free survival (DFS) in CC patients. Mechanistically, we showed that miR-24-3p downregulation contributes to TRIM11 upregulation in CC. We also demonstrated that TRIM11 overexpression promotes cell proliferation and colony formation and inhibits apoptosis in CC, while knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited cell proliferation and induced apoptosis. Silencing TRIM11 in vivo decreased tumor growth. These findings indicate that TRIM11 facilitates CC progression by promoting cell proliferation and inhibiting apoptosis and that the novel miR-24-3p/TRIM11 axis may be a useful new target for treating patients with CC.

Keywords: TRIM11; colon cancer; miR-24-3p.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • CRISPR-Cas Systems
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Mice, Nude
  • MicroRNAs / genetics*
  • Tripartite Motif Proteins / genetics*
  • Tumor Burden / genetics
  • Ubiquitin-Protein Ligases / genetics*
  • Xenograft Model Antitumor Assays / methods

Substances

  • MIRN24 microRNA, human
  • MicroRNAs
  • Tripartite Motif Proteins
  • TRIM11 protein, human
  • Ubiquitin-Protein Ligases