Overexpression of miR-10b in colorectal cancer patients: Correlation with TWIST-1 and E-cadherin expression

Tumour Biol. 2017 Mar;39(3):1010428317695916. doi: 10.1177/1010428317695916.

Abstract

MicroRNAs are emergent players of epigenetics that function as oncogenes or tumor suppressors and that have been implicated in regulating diverse cellular pathways. MiR-10b is an oncogenic microRNA involved in tumor invasion and metastasis in various cancers. Our data have shown that miR-10b is overexpressed in colorectal cancer samples in comparison with non-tumorous adjacent mucosa (p = 0.0025) and that it is associated with severe features such as tumor size >5 cm (p = 0.023), distant metastasis (p = 0.0022), non-differentiated tumors (p = 0.016), and vascular invasion (p = 0.01). Regarding the regulation of its expression, positive correlation between the loss of miR-10b and aberrant DNA methylation (p = 0.02) as well as a loss of TWIST-1 messenger RNA (p = 0.018) have been observed. Furthermore, expression analysis of the downstream miR-10b targets has shown that there are associations between low HOXD10 messenger RNA and E-cadherin protein levels (p < 0.0001, p = 0.0008, respectively) and overexpression of miR-10b. Our data suggests that overexpression of miR-10b results from high levels of TWIST-1 and may induce a decrease of E-cadherin membranous protein levels, thus contributing to the acquisition of metastatic phenotypes in colorectal cancer.

Keywords: E-cadherin; HOXD10; MiR-10b; TWIST-1; methylation; regulation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cadherins / biosynthesis*
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Female
  • HT29 Cells
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • RNA, Messenger / genetics
  • Transcription Factors / genetics*
  • Twist-Related Protein 1 / biosynthesis*
  • Twist-Related Protein 1 / genetics

Substances

  • Cadherins
  • Homeodomain Proteins
  • MIRN10 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Messenger
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1
  • HOXD10 protein, human