The mechanisms of colorectal cancer cell mesenchymal-epithelial transition induced by hepatocyte exosome-derived miR-203a-3p

BMC Cancer. 2021 Jun 19;21(1):718. doi: 10.1186/s12885-021-08419-x.

Abstract

Background: Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear.

Methods: Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET.

Results: In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells.

Coclusion: MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.

Keywords: Colorectal cancer; Exosome; Mesenchymal-to-epithelial transition; miR-203a-3p.

MeSH terms

  • Animals
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Congenital Hypothyroidism
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition
  • Exosomes / genetics*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Thyroid Dysgenesis

Substances

  • MIRN203 microRNA, human
  • MicroRNAs

Supplementary concepts

  • Hypothyroidism, Congenital, Nongoitrous, 2