MicroRNA-4461 derived from bone marrow mesenchymal stem cell exosomes inhibits tumorigenesis by downregulating COPB2 expression in colorectal cancer

Biosci Biotechnol Biochem. 2020 Feb;84(2):338-346. doi: 10.1080/09168451.2019.1677452. Epub 2019 Oct 21.

Abstract

Colorectal cancer (CRC) is one of the main cause of cancer-related deaths. It's reported that bone marrow mesenchymal stem cells (BMSCs) affects tumor development through secreting exosomes. This study aims to investigate the function of BMSCs-derived exosome miR-4461 in CRC. The results of qRT-PCR showed that miR-4461 expression in DLD1, HCT116 and SW480 CRC cells and CRC tissues was lower than that in FHC cells and normal tissues, respectively. And COPB2 mRNA expression was negatively correlated with miR-4461. Western blot was used to detect COPB2 protein expression. Dual-luciferase reporter assay results revealed that miR-4461 targeted COPB2. Transwell assay and CCK-8 assay demonstrated that COPB2 knockdown inhibited HCT116 and SW480 cells proliferation, migration and invasion abilities. Furthermore, BMSCs-derived exosome miR-4461 downregulated COPB2 expression and inhibited HCT116 and SW480 cells migration and invasion. The findings demonstrated that miR-4461 could be a potential target for the diagnosis and treatment of colorectal cancer.

Keywords: COPB2; Colorectal cancer; exosome; miR-4461; tumorigenesis.

MeSH terms

  • Bone Marrow Cells / metabolism*
  • Carcinogenesis*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Coatomer Protein / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Down-Regulation*
  • Exosomes / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness

Substances

  • COPB2 protein, human
  • Coatomer Protein
  • MIRN4461 microRNA, human
  • MicroRNAs