Extracellular vesicles carrying miR-193a derived from mesenchymal stem cells impede cell proliferation, migration and invasion of colon cancer by downregulating FAK

Exp Cell Res. 2020 Sep 15;394(2):112144. doi: 10.1016/j.yexcr.2020.112144. Epub 2020 Jun 12.

Abstract

MicroRNA (miR) deregulation is frequently seen in colon cancer. In this study, we sought to investigate biological effects of miR-193a on colon cancer and its underlying mechanism. Microarray analysis was conducted to obtain the differentially expressed miRs and their target genes in colon cancer. Bone-marrow derived mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) were obtained. The functional roles of miR-193a and FAK in colon cancer were determined using loss- and gain-function experiments. The cell proliferation, and migration and invasion were evaluated by CCK-8 and Transwell assay respectively. Dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-193a and FAK. Furthermore, in vivo experiment was conducted to test the roles of EV miR-193a in colon cancer growth, followed by determination of PCNA, MMP-2, and MMP-9 protein expression using Western blot analysis. MiR-193a was downregulated, whereas FAK was upregulated in colon cancer. MiR-193a upregulation or FAK downregulation inhibited proliferation, migration and invasion of colon cancer cells. miR-193a could downregulate FAK. Upregulation of EV miR-193a was observed to impede proliferation, migration and invasion of colon cancer cells in vitro and in vivo, accompanied by decreased PCNA, MMP-2, and MMP-9 expression. In summary, EV miR-193a derived from MSCs impeded colon cancer progression by targeting FAK, thus suggesting a new potential strategy for colon cancer treatment.

Keywords: Colon cancer; Focal adhesion kinase; Invasion; Metastasis; MicroRNA-193a; Migration; Proliferation.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology*
  • Down-Regulation / genetics*
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / ultrastructure
  • Focal Adhesion Protein-Tyrosine Kinases / genetics*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Models, Biological
  • Neoplasm Invasiveness
  • Up-Regulation / genetics

Substances

  • MIRN193 microRNA, human
  • MicroRNAs
  • Focal Adhesion Protein-Tyrosine Kinases