MicroRNA-128 inhibits EMT of human osteosarcoma cells by directly targeting integrin α2

Tumour Biol. 2016 Jun;37(6):7951-7. doi: 10.1007/s13277-015-4696-0. Epub 2015 Dec 24.

Abstract

Deregulated expression of miRNAs contributes to the development of osteosarcoma. The present study was to evaluate the level of miR-128 and integrin α2 (ITGA2) in osteosarcoma tissues and cells. We further investigated the molecular mechanisms of miR-128 and ITGA2 in osteosarcoma cell lines. In the present study, we found that miR-128 expression was down-regulated in osteosarcoma tissues and MG-63, U2OS, and SAOS-2 cells (all p < 0.001). By contrast, ITGA2 was up-regulated. Furthermore, we found that miR-128 overexpression suppressed cell migration and invasion of MG-63 cells. Mechanically, miR-128 overexpression inhibited epithelial-mesenchymal transition (EMT) of MG-63 cells. Importantly, we identified that the 3'-untranslated region (3'-UTR) of ITGA2 was a direct target of miR-128. Luciferase reporter assays confirmed that miR-128 binding to the 3'-UTR regions of ITGA2 inhibited the expression of ITGA2 in MG-63 cells. At the same time, overexpressed ITGA2 also reversed EMT inhibited by miR-128. In conclusion, this study suggested that high miR-128 expression suppressed osteosarcoma cell migration, invasion, and EMT development through targeting ITGA2, which may be recommended as a therapeutic target for osteosarcoma.

Keywords: EMT; ITGA2; Osteosarcoma; miR-128.

MeSH terms

  • Blotting, Western
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha2 / genetics
  • Integrin alpha2 / metabolism*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Wound Healing

Substances

  • Integrin alpha2
  • MIRN128 microRNA, human
  • MicroRNAs