ADAMTS8 inhibits glioma development in vitro and in vivo

Folia Neuropathol. 2023;61(2):144-152. doi: 10.5114/fn.2023.129380.

Abstract

Introduction: In recent years, novel RNAs have been revealed to be regulators in glioma. ADAMTS8 has been reported to be reduced in brain tumours. In this study, we aimed to explore the role of ADAMTS8 in glioma.

Material and methods: Online bioinformatic tools, Gepia and Chinese Glioma Genome Atlas database (CGGA) were used to analyse the differential expression of ADAMTS8, overall survival and disease-free survival rates and the correlations between ADAMTS8 and matrix metallopeptidases (MMP2 and MMP9) in glioma. RT-qPCR and western blot experiments were performed to measure the mRNA and protein expression. ADAMTS8 expression was regulated in cells through transfection. Thereafter, the effect of ADAMTS8 on cells was investigated through the cell viability, apoptosis and transwell experiments. The epithelial-mesenchymal transition (EMT)-related proteins and also MMP2 and MMP9 were examined. The subcutaneous tumour model was established to validate the suppressive role of ADAMTS8 in tumour growth.

Results: ADAMTS8 expression was reduced in glioma tissues and cells. Higher expression of ADAMTS8 was correlated with higher survival rates. ADAMTS8 was correlated with MMP2 and MMP9 in glioma tissues. In glioma cells, overexpression of ADAMTS8 could inhibit the viability, invasion, migration and EMT, and MMP2 and MMP9, but promote the apoptosis of cells. The upregulation of ADAMTS8 could inhibit the tumour growth in vivo.

Conclusions: ADAMTS8 was inhibited in glioma and the higher expression of ADAMTS8 might be related to better prognosis among glioma patients. Overexpression of ADAMTS8 inhibited the development of glioma in vitro and in vivo.

Keywords: ADAMTS8; EMT; brain tumour; survival rate; glioma.

MeSH terms

  • ADAMTS Proteins
  • Apoptosis
  • Brain Neoplasms* / genetics
  • Glioma* / genetics
  • Humans
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9

Substances

  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • ADAMTS8 protein, human
  • ADAMTS Proteins