Exosomal miR-99b-5p Secreted from Mesenchymal Stem Cells Can Retard the Progression of Colorectal Cancer by Targeting FGFR3

Stem Cell Rev Rep. 2023 Nov;19(8):2901-2917. doi: 10.1007/s12015-023-10606-1. Epub 2023 Aug 31.

Abstract

Human bone marrow mesenchymal stem cells (BMSCs) are efficient mass producers of exosomes that can potentially be utilized for delivery of miRNAs in cancer therapy. The current study aimed to assess the role of MSC-exosomal miR-99b-5p during the development of colorectal cancer (CRC). The potential value of using plasma levels of exosomal miR-99b-5p for predicting the liver metastasis of colorectal cancer was also assessed. In this study, we found that overexpression of fibroblast growth factor receptor 3 (FGFR3) was associated with tumor progression in CRC and FGFR3 was the target gene of miR-99b-5p, which was down-regulated in CRC tissues. Furthermore, we observed that elevated miR-99b-5p inhibited CRC cell proliferation, invasion and migration, while reduced levels had the opposite effect on CRC cells. Moreover, exosomal miR-99b-5p delivered by BMSCs was able to limit the proliferation, invasion and migration of CRC cells in vitro, as well as suppressing tumor growth in vivo. Collectively, these findings revealed that MSC-derived exosomal miR-99b-5p can be transferred into CRC cells and which can suppress tumor progression by targeting FGFR3. This highlights the potential of using exosomal miR-99b-5p as a novel diagnostic marker for CRC, while providing a therapeutic target to combat CRC.

Keywords: Colorectal cancer; Exosomes; FGFR3; Human bone marrow mesenchymal stem cells; miR-99b-5p.

MeSH terms

  • Colorectal Neoplasms* / genetics
  • Humans
  • Liver Neoplasms*
  • Mesenchymal Stem Cells*
  • MicroRNAs* / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics

Substances

  • Receptor, Fibroblast Growth Factor, Type 3
  • MicroRNAs
  • FGFR3 protein, human