Exosome microRNA-22 inhibiting proliferation, migration and invasion through regulating Twist1/CADM1 axis in osteosarcoma

Sci Rep. 2024 Jan 8;14(1):761. doi: 10.1038/s41598-023-50612-4.

Abstract

This study aims to the function of miR-22 original mesenchymal stem cells (MSC) on osteosarcoma (OS) proliferation, migration and invasion. Bio-informatics analysis including GEO2R analysis, Gene Ontology analysis, integration analysis were used to confirmed the target genes (miR-22, Twist1, CADM1) in OS. RT-qPCR and western blotting confirmed the different expression of miR-22, Twist1, CADM1 in OS tissues, MG63 and Saos cell lines. MTS assay, CCK8 assay, colony forming assay, EdU assay were performed to detect the proliferation effect of miR-22 on MG63. Transwell migration assay, transwell invasion assay, wound healing assay were used to verify the migration and invasion effect of miR-22 on MG63. Luciferase reporter assay confirm the binding sites between miR-22 and Twist1. RT-qPCR confirmed miR-22 and CADM1 downregulated and Twist1 upregulated in OS tissues, MG63 and Saos. Exosome original MSC labeled with PKH-26 could be uptake by MG63, which upregulated the expression of miR-22 in MG63. High expression of miR-22 in MG63 inhibited proliferation, migration and invasion, which could be rescued by Twist1. Dual luciferase reporter analysis confirmed Twist1 was a target of miR-22. Exosome modified with miR-22 mimic inhibit proliferation, migration and invasion more efficient than exosome original MSC. miR-22 cargo in exo-MSC could uptake by MG63 and supply MG63 with miR-22, which inhibit MG63 proliferation, migration and invasion through targeting Twist1.

MeSH terms

  • Bone Neoplasms* / genetics
  • Cell Adhesion Molecule-1 / genetics
  • Cell Proliferation / genetics
  • Exosomes* / genetics
  • Humans
  • Luciferases
  • MicroRNAs* / genetics
  • Osteosarcoma* / genetics

Substances

  • Luciferases
  • MicroRNAs
  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • MIRN22 microRNA, human

Supplementary concepts

  • Elliptocytosis 4